Novel human proteases and polynucleotides encoding the same

ABSTRACT

Novel human polynucleotide and polypeptide sequences are disclosed that can be used in therapeutic, diagnostic, and pharmacogenomic applications.

[0001] The present application claims the benefit of U.S. Provisional Application Numbers 60/227,104 and 60/233,796 which were filed on Aug. 22, 2000 and Sep. 19, 2000, respectively. These U.S. Provisional Applications are herein incorporated by reference in their entirety.

1. INTRODUCTION

[0002] The present invention relates to the discovery, identification, and characterization of novel human polynucleotides encoding proteins sharing sequence similarity with mammalian proteases. The invention encompasses the described polynucleotides, host cell expression systems, the encoded proteins, fusion proteins, polypeptides and peptides, antibodies to the encoded proteins and peptides, and genetically engineered animals that either lack or over express the disclosed sequences, antagonists and agonists of the proteins, and other compounds that modulate the expression or activity of the proteins encoded by the disclosed polynucleotides that can be used for diagnosis, drug screening, clinical trial monitoring, the treatment of diseases and disorders, and cosmetic or nutriceutical applications.

2. BACKGROUND OF THE INVENTION

[0003] Proteases cleave protein substrates as part of degradation, maturation, and secretory pathways within the body. Proteases have been associated with, inter alia, regulating development, diabetes, obesity, infertility, modulating cellular processes, and infectious disease.

3. SUMMARY OF THE INVENTION

[0004] The present invention relates to the discovery, identification, and characterization of nucleotides that encode novel human proteins, and the corresponding amino acid sequences of these proteins. The novel human proteins (NHPs) described for the first time herein share structural similarity with animal proteases and particularly zinc metalloproteases.

[0005] The novel human nucleic acid (cDNA) sequences described herein, encode proteins/open reading frames (ORFs) of 451, 297, 486, 1222, 1219, 1216, 1213, 1235, 1232, 1252, 1249, and 1907 amino acids in length (see SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 25 respectively).

[0006] The invention also encompasses agonists and antagonists of the described NHPS, including small molecules, large molecules, mutant NHPs, or portions thereof, that compete with native NHP, peptides, and antibodies, as well as nucleotide sequences that can be used to inhibit the expression of the described NHPs (e.g., antisense and ribozyme molecules, and open reading frame or regulatory sequence replacement constructs) or to enhance the expression of the described NHPs (e.g., expression constructs that place the described polynucleotide under the control of a strong promoter system), and transgenic animals that express a NHP sequence, or “knock-outs” (which can be conditional) that do not express a functional NHP. Knock-out mice can be produced in several ways, one of which involves the use of mouse embryonic stem cells (“ES cells”) lines that contain gene trap mutations in a murine homolog of at least one of the described NHPs. When the unique NHP sequences described in SEQ ID NOS:1-26 are “knocked-out” they provide a method of identifying phenotypic expression of the particular gene as well as a method of assigning function to previously unknown genes. In addition, animals in which the unique NHP sequences described in SEQ ID NOS:1-26 are “knocked-out” provide a unique source in which to elicit antibodies to homologous and orthologous proteins which would have been previously viewed by the immune system as “self” and therefore would have failed to elicit significant antibody responses. To these ends, gene trapped knockout ES cells have been generated in murine homologs of the described NHPS.

[0007] Additionally, the unique NHP sequences described in SEQ ID NOS:1-26 are useful for the identification of protein coding sequence and mapping a unique gene to a particular chromosome. These sequences identify actual, biologically relevant, exon splice junctions as opposed to those that might have been predicted bioinformatically from genomic sequence alone.

[0008] Further, the present invention also relates to processes for identifying compounds that modulate, i.e., act as agonists or antagonists, of NHP expression and/or NHP activity that utilize purified preparations of the described NHPs and/or NHP product, or cells expressing the same. Such compounds can be used as therapeutic agents for the treatment of any of a wide variety of symptoms associated with biological disorders or imbalances.

4. DESCRIPTION OF THE SEQUENCE LISTING AND FIGURES

[0009] The Sequence Listing provides the sequences of several NHP ORFs encoding the described NHP amino acid sequences. SEQ ID NOS:23 and 26 describe NHP ORFs and flanking sequences.

5. DETAILED DESCRIPTION OF THE INVENTION

[0010] The NHP sequences described for the first time herein are novel proteins that are expressed in, inter alia, human cell lines, and human spinal cord, lymph node, bone marrow, trachea, mammary gland, skeletal muscle, pericardium, adipose, esophagus, bladder, fetal kidney, and fetal lung cells (SEQ ID NOS:1-23), and the NHP sequences identified in SEQ ID NOS: 24-26 may be predominantly expressed in heart, fetal kidney and fetal lung.

[0011] The described sequences were compiled from cDNA clones, genomic sequence, and cDNAs derived from human lymph node, thyroid, fetal brain, bone marrow, trachea, kidney, and mammary gland mRNAs (Edge Biosystems, Gaithersburg, Md., and Clontech, Palo Alto, Calif.). The present invention encompasses the nucleotides presented in the Sequence Listing, host cells expressing such nucleotides, the expression products of such nucleotides, and: (a) nucleotides that encode mammalian homologs of the described genes, including the specifically described NHPs, and NHP products; (b) nucleotides that encode one or more portions of a NHP that correspond to functional domains, and the polypeptide products specified by such nucleotide sequences, including but not limited to the novel regions of any active domain(s); (c) isolated nucleotides that encode mutant versions, engineered or naturally occurring, of the described NHPs in which all or a part of at least one domain is deleted or altered, and the polypeptide products specified by such nucleotide sequences, including but not limited to soluble proteins and peptides in which all or a portion of the signal sequence is deleted; (d) nucleotides that encode chimeric fusion proteins containing all or a portion of a coding region of a NHP, or one of its domains (e.g., a receptor or ligand binding domain, accessory protein/self-association domain, etc.) fused to another peptide or polypeptide; or (e) therapeutic or diagnostic derivatives of the described polynucleotides such as oligonucleotides, antisense polynucleotides, ribozymes, dsRNA, or gene therapy constructs comprising a sequence first disclosed in the Sequence Listing.

[0012] As discussed above, the present invention includes: (a) the human DNA sequences presented in the Sequence Listing (and vectors comprising the same) and additionally contemplates any nucleotide sequence encoding a contiguous NHP open reading frame (ORF), or a contiguous exon splice junction first described in the Sequence Listing, that hybridizes to a complement of a DNA sequence presented in the Sequence Listing under highly stringent conditions, e.g., hybridization to filter-bound DNA in 0.5 M NaHPO₄, 7% sodium dodecyl sulfate (SDS), 1 mM EDTA at 65° C., and washing in 0.1×SSC/0.1% SDS at 68° C. (Ausubel F. M. et al., eds., 1989, Current Protocols in Molecular Biology, Vol. I, Green Publishing Associates, Inc., and John Wiley & Sons, Inc., NY, at p. 2.10.3) and encodes a functionally equivalent expression product. Additionally contemplated are any nucleotide sequences that hybridize to the complement of the DNA sequence that encode and express an amino acid sequence presented in the Sequence Listing under moderately stringent conditions, e.g., washing in 0.2×SSC/0.1% SDS at 42° C. (Ausubel et al., 1989, supra), yet still encode a functionally equivalent NHP product. Functional equivalents of a NHP include naturally occurring NHPs present in other species and mutant NHPs whether naturally occurring or engineered (by site directed mutagenesis, gene shuffling, directed evolution as described in, for example, U.S. Pat. No. 5,837,458). The invention also includes degenerate nucleic acid variants of the disclosed NHP polynucleotide sequences.

[0013] Additionally contemplated are polynucleotides encoding a NHP ORF, or its functional equivalent, encoded by a polynucleotide sequence that is about 99, 95, 90, or about 85 percent similar or identical to corresponding regions of the nucleotide sequences of the Sequence Listing (as measured by BLAST sequence comparison analysis using, for example, the GCG sequence analysis package using standard default settings).

[0014] The invention also includes nucleic acid molecules, preferably DNA molecules, that hybridize to, and are therefore the complements of, the described NHP gene nucleotide sequences. Such hybridization conditions may be highly stringent or less highly stringent, as described above. In instances where the nucleic acid molecules are deoxyoligonucleotides (“DNA oligos”), such molecules are generally about 16 to about 100 bases long, or about 20 to about 80, or about 34 to about 45 bases long, or any variation or combination of sizes represented therein that incorporate a contiguous region of sequence first disclosed in the Sequence Listing. Such oligonucleotides can be used in conjunction with the polymerase chain reaction (PCR) to screen libraries, isolate clones, and prepare cloning and sequencing templates, etc.

[0015] Alternatively, such NHP oligonucleotides can be used as hybridization probes for screening libraries, and assessing gene expression patterns (particularly using a micro array or high-throughput “chip” format). Additionally, a series of the described NHP oligonucleotide sequences, or the complements thereof, can be used to represent all or a portion of the described NHP sequences. An oligonucleotide or polynucleotide sequence first disclosed in at least a portion of one or more of the sequences of SEQ ID NOS: 1-26 can be used as a hybridization probe in conjunction with a solid support matrix/substrate (resins, beads, membranes, plastics, polymers, metal or metallized substrates, crystalline or polycrystalline substrates, etc.). Of particular note are spatially addressable arrays (i.e., gene chips, microtiter plates, etc.) of oligonucleotides and polynucleotides, or corresponding oligopeptides and polypeptides, wherein at least one of the biopolymers present on the spatially addressable array comprises an oligonucleotide or polynucleotide sequence first disclosed in at least one of the sequences of SEQ ID NOS: 1-26, or an amino acid sequence encoded thereby. Methods for attaching biopolymers to, or synthesizing biopolymers on, solid support matrices, and conducting binding studies thereon are disclosed in, inter alia, U.S. Pat. Nos. 5,700,637, 5,556,752, 5,744,305, 4,631,211, 5,445,934, 5,252,743, 4,713,326, 5,424,186, and 4,689,405 the disclosures of which are herein incorporated by reference in their entirety.

[0016] Addressable arrays comprising sequences first disclosed in SEQ ID NOS:1-26 can be used to identify and characterize the temporal and tissue specific expression of a gene. These addressable arrays incorporate oligonucleotide sequences of sufficient length to confer the required specificity, yet be within the limitations of the production technology. The length of these probes is within a range of between about 8 to about 2000 nucleotides. Preferably the probes consist of 60 nucleotides and more preferably 25 nucleotides from the sequences first disclosed in SEQ ID NOS:1-26.

[0017] For example, a series of the described oligonucleotide sequences, or the complements thereof, can be used in chip format to represent all or a portion of the described sequences. The oligonucleotides, typically between about 16 to about 40 (or any whole number within the stated range) nucleotides in length can partially overlap each other and/or the sequence may be represented using oligonucleotides that do not overlap. Accordingly, the described polynucleotide sequences shall typically comprise at least about two or three distinct oligonucleotide sequences of at least about 8 nucleotides in length that are each first disclosed in the described Sequence Listing. Such oligonucleotide sequences can begin at any nucleotide present within a sequence in the Sequence Listing and proceed in either a sense (5′-to-3′) orientation vis-a-vis the described sequence or in an antisense orientation.

[0018] Microarray-based analysis allows the discovery of broad patterns of genetic activity, providing new understanding of gene functions and generating novel and unexpected insight into transcriptional processes and biological mechanisms. The use of addressable arrays comprising sequences first disclosed in SEQ ID NOS:1-26 provides detailed information about transcriptional changes involved in a specific pathway, potentially leading to the identification of novel components or gene functions that manifest themselves as novel phenotypes.

[0019] Probes consisting of sequences first disclosed in SEQ ID NOS:1-26 can also be used in the identification, selection and validation of novel molecular targets for drug discovery. The use of these unique sequences permits the direct confirmation of drug targets and recognition of drug dependent changes in gene expression that are modulated through pathways distinct from the drugs intended target. These unique sequences therefore also have utility in defining and monitoring both drug action and toxicity.

[0020] As an example of utility, the sequences first disclosed in SEQ ID NOS:1-26 can be utilized in microarrays or other assay formats, to screen collections of genetic material from patients who have a particular medical condition. These investigations can also be carried out using the sequences first disclosed in SEQ ID NOS:1-26 in silico and by comparing previously collected genetic databases and the disclosed sequences using computer software known to those in the art.

[0021] Thus the sequences first disclosed in SEQ ID NOS:1-26 can be used to identify mutations associated with a particular disease and also as a diagnostic or prognostic assay.

[0022] Although the presently described sequences have been specifically described using nucleotide sequence, it should be appreciated that each of the sequences can uniquely be described using any of a wide variety of additional structural attributes, or combinations thereof. For example, a given sequence can be described by the net composition of the nucleotides present within a given region of the sequence in conjunction with the presence of one or more specific oligonucleotide sequence(s) first disclosed in the SEQ ID NOS: 1-26. Alternatively, a restriction map specifying the relative positions of restriction endonuclease digestion sites, or various palindromic or other specific oligonucleotide sequences can be used to structurally describe a given sequence. Such restriction maps, which are typically generated by widely available computer programs (e.g., the University of Wisconsin GCG sequence analysis package, SEQUENCHER 3.0, Gene Codes Corp., Ann Arbor, Mich., etc.), can optionally be used in conjunction with one or more discrete nucleotide sequence(s) present in the sequence that can be described by the relative position of the sequence relative to one or more additional sequence(s) or one or more restriction sites present in the disclosed sequence.

[0023] For oligonucleotide probes, highly stringent conditions may refer, e.g., to washing in 6×SSC/0.05% sodium pyrophosphate at 37° C. (for 14-base oligos), 48° C. (for 17-base oligos), 55° C. (for 20-base oligos), and 60° C. (for 23-base oligos). These nucleic acid molecules may encode or act as NHP gene antisense molecules, useful, for example, in NHP gene regulation (for and/or as antisense primers in amplification reactions of NHP gene nucleic acid sequences). With respect to NHP gene regulation, such techniques can be used to regulate biological functions. Further, such sequences may be used as part of ribozyme and/or triple helix sequences that are also useful for NHP gene regulation.

[0024] Inhibitory antisense or double stranded oligonucleotides can additionally comprise at least one modified base moiety which is selected from the group including but not limited to 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xantine, 4-acetylcytosine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, beta-D-mannosylqueosine, 5′-methoxycarboxymethyluracil, 5-methoxyuracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 2-thiouracil, 4-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3)w, and 2,6-diaminopurine.

[0025] The antisense oligonucleotide can also comprise at least one modified sugar moiety selected from the group including but not limited to arabinose, 2-fluoroarabinose, xylulose, and hexose.

[0026] In yet another embodiment, the antisense oligonucleotide will comprise at least one modified phosphate backbone selected from the group consisting of a phosphorothioate, a phosphorodithioate, a phosphoramidothioate, a phosphoramidate, a phosphordiamidate, a methylphosphonate, an alkyl phosphotriester, and a formacetal or analog thereof.

[0027] In yet another embodiment, the antisense oligonucleotide is an α-anomeric oligonucleotide. An α-anomeric oligonucleotide forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual β-units, the strands run parallel to each other (Gautier et al., 1987, Nucl. Acids Res. 15:6625-6641). The oligonucleotide is a 2′-0-methylribonucleotide (Inoue et al., 1987, Nucl. Acids Res. 15:6131-6148), or a chimeric RNA-DNA analogue (Inoue et al., 1987, FEBS Lett. 215:327-330). Alternatively, double stranded RNA can be used to disrupt the expression and function of a targeted NHP.

[0028] Oligonucleotides of the invention can be synthesized by standard methods known in the art, e.g. by use of an automated DNA synthesizer (such as are commercially available from Biosearch, Applied Biosystems, etc.). As examples, phosphorothioate oligonucleotides can be synthesized by the method of Stein et al. (1988, Nucl. Acids Res. 16:3209), and methylphosphonate oligonucleotides can be prepared by use of controlled pore glass polymer supports (Sarin et al., 1988, Proc. Natl. Acad. Sci. U.S.A. 85:7448-7451), etc.

[0029] Low stringency conditions are well known to those of skill in the art, and will vary predictably depending on the specific organisms from which the library and the labeled sequences are derived. For guidance regarding such conditions see, for example, Sambrook et al., 1989, Molecular Cloning, A Laboratory Manual (and periodic updates thereof), Cold Springs Harbor Press, NY; and Ausubel et al., 1989, Current Protocols in Molecular Biology, Green Publishing Associates and Wiley Interscience, N.Y.

[0030] Alternatively, suitably labeled NHP nucleotide probes can be used to screen a human genomic library using appropriately stringent conditions or by PCR. The identification and characterization of human genomic clones is helpful for identifying polymorphisms (including, but not limited to, nucleotide repeats, microsatellite alleles, single nucleotide polymorphisms, or coding single nucleotide polymorphisms), determining the genomic structure of a given locus/allele, and designing diagnostic tests. For example, sequences derived from regions adjacent to the intron/exon boundaries of the human gene can be used to design primers for use in amplification assays to detect mutations within the exons, introns, splice sites (e.g., splice acceptor and/or donor sites), etc., that can be used in diagnostics and pharmacogenomics.

[0031] Further, a NHP homolog can be isolated from nucleic acid from an organism of interest by performing PCR using two degenerate or “wobble” oligonucleotide primer pools designed on the basis of amino acid sequences within the NHP products disclosed herein. The template for the reaction may be total RNA, mRNA, and/or cDNA obtained by reverse transcription of mRNA prepared from human or non-human cell lines or tissue known or suspected to express an allele of a NHP gene. The PCR product can be subcloned and sequenced to ensure that the amplified sequences represent the sequence of the desired NHP gene. The PCR fragment can then be used to isolate a full length cDNA clone by a variety of methods. For example, the amplified fragment can be labeled and used to screen a cDNA library, such as a bacteriophage cDNA library. Alternatively, the labeled fragment can be used to isolate genomic clones via the screening of a genomic library.

[0032] PCR technology can also be used to isolate full length cDNA sequences. For example, RNA can be isolated, following standard procedures, from an appropriate cellular or tissue source (i.e., one known, or suspected, to express a NHP gene, such as, for example, testis tissue). A reverse transcription (RT) reaction can be performed on the RNA using an oligonucleotide primer specific for the most 5′ end of the amplified fragment for the priming of first strand synthesis. The resulting RNA/DNA hybrid may then be “tailed” using a standard terminal transferase reaction, the hybrid may be digested with RNase H, and second strand synthesis may then be primed with a complementary primer. Thus, cDNA sequences upstream of the amplified fragment can be isolated. For a review of cloning strategies that can be used, see e.g., Sambrook et al., 1989, supra.

[0033] A cDNA encoding a mutant NHP sequence can be isolated, for example, by using PCR. In this case, the first cDNA strand may be synthesized by hybridizing an oligo-dT oligonucleotide to mRNA isolated from tissue known or suspected to be expressed in an individual putatively carrying a mutant NHP allele, and by extending the new strand with reverse transcriptase. The second strand of the cDNA is then synthesized using an oligonucleotide that hybridizes specifically to the 5′ end of the normal sequence. Using these two primers, the product is then amplified via PCR, optionally cloned into a suitable vector, and subjected to DNA sequence analysis through methods well known to those of skill in the art. By comparing the DNA sequence of the mutant NHP allele to that of a corresponding normal NHP allele, the mutation(s) responsible for the loss or alteration of function of the mutant NHP gene product can be ascertained.

[0034] Alternatively, a genomic library can be constructed using DNA obtained from an individual suspected of or known to carry a mutant NHP allele (e.g., a person manifesting a NHP-associated phenotype such as, for example, obesity, high blood pressure, arthritis, connective tissue disorders, infertility, etc.), or a cDNA library can be constructed using RNA from a tissue known, or suspected, to express a mutant NHP allele. A normal NHP gene, or any suitable fragment thereof, can then be labeled and used as a probe to identify the corresponding mutant NHP allele in such libraries. Clones containing mutant NHP sequences can then be purified and subjected to sequence analysis according to methods well known to those skilled in the art.

[0035] Additionally, an expression library can be constructed utilizing cDNA synthesized from, for example, RNA isolated from a tissue known, or suspected, to express a mutant NHP allele in an individual suspected of or known to carry such a mutant allele. In this manner, gene products made by the putatively mutant tissue can be expressed and screened using standard antibody screening techniques in conjunction with antibodies raised against normal NHP product, as described below (for screening techniques, see, for example, Harlow, E. and Lane, eds., 1988, “Antibodies: A Laboratory Manual”, Cold Spring Harbor Press, Cold Spring Harbor, N.Y.).

[0036] Additionally, screening can be accomplished by screening with labeled NHP fusion proteins, such as, for example, alkaline phosphatase-NHP or NHP-alkaline phosphatase fusion proteins. In cases where a NHP mutation results in an expression product with altered function (e.g., as a result of a missense or a frameshift mutation), polyclonal antibodies to NHP are likely to cross-react with a corresponding mutant NHP expression product. Library clones detected via their reaction with such labeled antibodies can be purified and subjected to sequence analysis according to methods well known in the art.

[0037] The invention also encompasses (a) DNA vectors that contain any of the foregoing NHP coding sequences and/or their complements (i.e., antisense); (b) DNA expression vectors that contain any of the foregoing NHP coding sequences operatively associated with a regulatory element that directs the expression of the coding sequences (for example, baculo virus as described in U.S. Pat. No. 5,869,336 herein incorporated by reference); (c) genetically engineered host cells that contain any of the foregoing NHP coding sequences operatively associated with a regulatory element that directs the expression of the coding sequences in the host cell; and (d) genetically engineered host cells that express an endogenous NHP sequence under the control of an exogenously introduced regulatory element (i.e., gene activation) or genetically engineered transcription factor. As used herein, regulatory elements include, but are not limited to, inducible and non-inducible promoters, enhancers, operators and other elements known to those skilled in the art that drive and regulate expression. Such regulatory elements include but are not limited to the cytomegalovirus (hCMV) immediate early gene, regulatable, viral elements (particularly retroviral LTR promoters), the early or late promoters of SV40 adenovirus, the lac system, the trp system, the TAC system, the TRC system, the major operator and promoter regions of phage lambda, the control regions of fd coat protein, the promoter for 3-phosphoglycerate kinase (PGK), the promoters of acid phosphatase, and the promoters of the yeast α-mating factors.

[0038] The present invention also encompasses antibodies and anti-idiotypic antibodies (including Fab fragments), antagonists and agonists of a NHP, as well as compounds or nucleotide constructs that inhibit expression of a NHP sequence (transcription factor inhibitors, antisense and ribozyme molecules, or open reading frame sequence or regulatory sequence replacement constructs), or promote the expression of a NHP (e.g., expression constructs in which NHP coding sequences are operatively associated with expression control elements such as promoters, promoter/enhancers, etc.).

[0039] The NHPs or NHP peptides, NHP fusion proteins, NHP nucleotide sequences, antibodies, antagonists and agonists can be useful for the detection of mutant NHPs or inappropriately expressed NHPs for the diagnosis of disease. The NHPs or NHP peptides, NHP fusion proteins, NHP nucleotide sequences, host cell expression systems, antibodies, antagonists, agonists and genetically engineered cells and animals can be used for screening for drugs (or high throughput screening of combinatorial libraries) effective in the treatment of the symptomatic or phenotypic manifestations of perturbing the normal function of NHP in the body. The use of engineered host cells and/or animals may offer an advantage in that such systems allow not only for the identification of compounds that bind to the endogenous receptor for a NHP, but can also identify compounds that trigger NHP-mediated activities or pathways.

[0040] Finally, the NHP products can be used as therapeutics. For example, soluble derivatives such as NHP peptides/domains corresponding to NHP, NHP fusion protein products (especially NHP-Ig fusion proteins, i.e., fusions of a NHP, or a domain of a NHP, to an IgFc), NHP antibodies and anti-idiotypic antibodies (including Fab fragments), antagonists or agonists (including compounds that modulate or act on downstream targets in a NHP-mediated pathway) can be used to directly treat diseases or disorders. For instance, the administration of an effective amount of soluble NHP, or a NHP-IgFc fusion protein or an anti-idiotypic antibody (or its Fab) that mimics a NHP could activate or effectively antagonize the endogenous NHP receptor. Nucleotide constructs encoding such NHP products can be used to genetically engineer host cells to express such products in vivo; these genetically engineered cells function as “bioreactors” in the body delivering a continuous supply of a NHP, a NHP peptide, or a NHP fusion protein to the body. Nucleotide constructs encoding functional NHP, mutant NHPs, as well as antisense and ribozyme molecules can also be used in “gene therapy” approaches for the modulation of NHP expression. Thus, the invention also encompasses pharmaceutical formulations and methods for treating biological disorders.

[0041] Various aspects of the invention are described in greater detail in the subsections below.

[0042] 5.1 The NHP Sequences

[0043] The cDNA sequences and corresponding deduced amino acid sequences of the described NHPs are presented in the Sequence Listing. The NHP nucleotides were obtained from human cDNA libraries using probes and/or primers generated from human genomic sequence. Expression analysis has provided evidence that the described NHP can be expressed a variety of human cells.

[0044] Several polymorphisms were identified including a A/G at the nucleotide position represented by, for example, position 58 of SEQ ID NO: 7 (which can result in a thr or ala at the region corresponding to amino acid (aa) position 20 of, for example, SEQ ID NO:8), a A/C at nucleotide position 1538 (which can result in a pro or gln at aa position 513), a C/T at position 1769 (which can result in an pro or leu at aa position 590), and a C/G at nucleotide position 1899 (which can result in a ser or arg at aa position 633).

[0045] An additional application of the described novel human polynucleotide sequences is their use in the molecular mutagenesis/evolution of proteins that are at least partially encoded by the described novel sequences using, for example, polynucleotide shuffling or related methodologies. Such approaches are described in U.S. Pat. Nos. 5,830,721 and 5,837,458 which are herein incorporated by reference in their entirety.

[0046] NHP gene products can also be expressed in transgenic animals. Animals of any species, including, but not limited to, worms, mice, rats, rabbits, guinea pigs, pigs, micro-pigs, birds, goats, and non-human primates, e.g., baboons, monkeys, and chimpanzees may be used to generate NHP transgenic animals.

[0047] Any technique known in the art may be used to introduce a NHP transgene into animals to produce the founder lines of transgenic animals. Such techniques include, but are not limited to pronuclear microinjection (Hoppe, P. C. and Wagner, T. E., 1989, U.S. Pat. No. 4,873,191); retrovirus mediated gene transfer into germ lines (Van der Putten et al., 1985, Proc. Natl. Acad. Sci., USA 82:6148-6152); gene targeting in embryonic stem cells (Thompson et al., 1989, Cell 56:313-321); electroporation of embryos (Lo, 1983, Mol Cell. Biol. 3:1803-1814); and sperm-mediated gene transfer (Lavitrano et al., 1989, Cell 57:717-723); etc. For a review of such techniques, see Gordon, 1989, Transgenic Animals, Intl. Rev. Cytol. 115:171-229, which is incorporated by reference herein in its entirety.

[0048] The present invention provides for transgenic animals that carry the NHP transgene in all their cells, as well as animals which carry the transgene in some, but not all their cells, i.e., mosaic animals or somatic cell transgenic animals. The transgene may be integrated as a single transgene or in concatamers, e.g., head-to-head tandems or head-to-tail tandems. The transgene may also be selectively introduced into and activated in a particular cell type by following, for example, the teaching of Lasko et al., 1992, Proc. Natl. Acad. Sci. USA 89:6232-6236. The regulatory sequences required for such a cell-type specific activation will depend upon the particular cell type of interest, and will be apparent to those of skill in the art.

[0049] When it is desired that a NHP transgene be integrated into the chromosomal site of the endogenous NHP gene, gene targeting is preferred. Briefly, when such a technique is to be utilized, vectors containing some nucleotide sequences homologous to the endogenous NHP gene are designed for the purpose of integrating, via homologous recombination with chromosomal sequences, into and disrupting the function of the nucleotide sequence of the endogenous NHP gene (i.e., “knockout” animals).

[0050] The transgene can also be selectively introduced into a particular cell type, thus inactivating the endogenous NHP gene in only that cell type, by following, for example, the teaching of Gu et al., 1994, Science, 265:103-106. The regulatory sequences required for such a cell-type specific inactivation will depend upon the particular cell type of interest, and will be apparent to those of skill in the art.

[0051] Once transgenic animals have been generated, the expression of the recombinant NHP gene may be assayed utilizing standard techniques. Initial screening may be accomplished by Southern blot analysis or PCR techniques to analyze animal tissues to assay whether integration of the transgene has taken place. The level of mRNA expression of the transgene in the tissues of the transgenic animals may also be assessed using techniques which include but are not limited to Northern blot analysis of tissue samples obtained from the animal, in situ hybridization analysis, and RT-PCR. Samples of NHP gene-expressing tissue, may also be evaluated immunocytochemically using antibodies specific for the NHP transgene product.

[0052] 5.2 NHPS and NHP Polypeptides

[0053] The NHPs, NHP polypeptides, NHP peptide fragments, mutated, truncated, or deleted forms of NHP, and/or NHP fusion proteins can be prepared for a variety of uses. These uses include but are not limited to the generation of antibodies, as reagents in diagnostic assays, the identification of other cellular gene products related to a NHP, as reagents in assays for screening for compounds that can be used as pharmaceutical reagents useful in the therapeutic treatment of mental, biological, or medical disorders and disease. The described NHPs share similarity with a variety of proteases, including, but not limited to, proteases having thrombospondin repeats, disintegrins, aggrecanases, procollagen I N-proteinase, and metalloproteinases (especially zinc metalloproteases of the ADAMTS family).

[0054] The Sequence Listing discloses the amino acid sequences encoded by the described NHP polynucleotides. The NHPs display initiator methionines in DNA sequence contexts consistent with translation initiation sites, and the ORFs display signal-like sequences which can indicate that the described NHP ORFs are secreted proteins or can be membrane associated.

[0055] The NHP amino acid sequences of the invention include the amino acid sequences presented in the Sequence Listing as well as analogues and derivatives thereof. Further, corresponding NHP homologues from other species are encompassed by the invention. In fact, any NHPs encoded by a NHP nucleotide sequence described above are within the scope of the invention, as are any novel polynucleotide sequences encoding all or any novel portion of an amino acid sequence presented in the Sequence Listing. The degenerate nature of the genetic code is well known, and, accordingly, each amino acid presented in the Sequence Listing, is generically representative of the well known nucleic acid “triplet” codon, or in many cases codons, that can encode the amino acid. As such, as contemplated herein, the amino acid sequences presented in the Sequence Listing, when taken together with the genetic code (see, for example, Table 4-1 at page 109 of “Molecular Cell Biology”, 1986, J. Darnell et al. eds., Scientific American Books, New York, N.Y., herein incorporated by reference) are generically representative of all the various permutations and combinations of nucleic acid sequences that can encode such amino acid sequences.

[0056] The invention also encompasses proteins that are functionally equivalent to the NHPs encoded by the presently described nucleotide sequences as judged by any of a number of criteria, including, but not limited to, the ability to bind and cleave a substrate of a NHP, or the ability to effect an identical or complementary downstream pathway, or a change in cellular metabolism (e.g., proteolytic activity, ion flux, tyrosine phosphorylation, etc.). Such functionally equivalent NHP proteins include, but are not limited to, additions or substitutions of amino acid residues within the amino acid sequence encoded by the NHP nucleotide sequences described above, but which result in a silent change, thus producing a functionally equivalent expression product. Amino acid substitutions can be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity, and/or the amphipathic nature of the residues involved. For example, nonpolar (hydrophobic) amino acids include alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan, and methionine; polar neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine, and glutamine; positively charged (basic) amino acids include arginine, lysine, and histidine; and negatively charged (acidic) amino acids include aspartic acid and glutamic acid.

[0057] A variety of host-expression vector systems can be used to express the NHP nucleotide sequences of the invention. Where, as in the present instance, a NHP peptide or NHP polypeptide is thought to be a soluble or secreted molecule, the peptide or polypeptide can be recovered from the culture media. Such expression systems also encompass engineered host cells that express NHP, or functional equivalent, in situ. Purification or enrichment of a NHP from such expression systems can be accomplished using appropriate detergents and lipid micelles and methods well known to those skilled in the art. However, such engineered host cells themselves may be used in situations where it is important not only to retain the structural and functional characteristics of a NHP, but to assess biological activity, e.g., in drug screening assays.

[0058] The expression systems that may be used for purposes of the invention include but are not limited to microorganisms such as bacteria (e.g., E. coli, B. subtilis) transformed with recombinant bacteriophage DNA, plasmid DNA or cosmid DNA expression vectors containing NHP nucleotide sequences; yeast (e.g., Saccharomyces, Pichia) transformed with recombinant yeast expression vectors containing NHP encoding nucleotide sequences; insect cell systems infected with recombinant virus expression vectors (e.g., baculovirus) containing NHP sequences; plant cell systems infected with recombinant virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or transformed with recombinant plasmid expression vectors (e.g., Ti plasmid) containing NHP nucleotide sequences; or mammalian cell systems (e.g., COS, CHO, BHK, 293, 3T3) harboring recombinant expression constructs containing promoters derived from the genome of mammalian cells (e.g., metallothionein promoter) or from mammalian viruses (e.g., the adenovirus late promoter; the vaccinia virus 7.5K promoter).

[0059] In bacterial systems, a number of expression vectors may be advantageously selected depending upon the use intended for the NHP product being expressed. For example, when a large quantity of such a protein is to be produced for the generation of pharmaceutical compositions of and/or containing a NHP, or for raising antibodies to a NHP, vectors that direct the expression of high levels of fusion protein products that are readily purified may be desirable. Such vectors include, but are not limited, to the E. coli expression vector pUR278 (Ruther et al., 1983, EMBO J. 2:1791), in which a NHP coding sequence may be ligated individually into the vector in frame with the lacZ coding region so that a fusion protein is produced; pIN vectors (Inouye & Inouye, 1985, Nucleic Acids Res. 13:3101-3109; Van Heeke & Schuster, 1989, J. Biol. Chem. 264:5503-5509); and the like. pGEX vectors (Pharmacia or American Type Culture Collection) can also be used to express foreign polypeptides as fusion proteins with glutathione S-transferase (GST). In general, such fusion proteins are soluble and can easily be purified from lysed cells by adsorption to glutathione-agarose beads followed by elution in the presence of free glutathione. The PGEX vectors are designed to include thrombin or factor Xa protease cleavage sites so that the cloned target expression product can be released from the GST moiety.

[0060] In an insect system, Autographa californica nuclear polyhedrosis virus (AcNPV) is used as a vector to express foreign polynucleotide seqeunces. The virus grows in Spodoptera frugiperda cells. A NHP coding sequence can be cloned individually into non-essential regions (for example the polyhedrin gene) of the virus and placed under control of an AcNPV promoter (for example the polyhedrin promoter). Successful insertion of NHP coding sequence will result in inactivation of the polyhedrin gene and production of non-occluded recombinant virus (i.e., virus lacking the proteinaceous coat coded for by the polyhedrin gene). These recombinant viruses are then used to infect Spodoptera frugiperda cells in which the inserted sequence is expressed (e.g., see Smith et al., 1983, J. Virol. 46: 584; Smith, U.S. Pat. No. 4,215,051).

[0061] In mammalian host cells, a number of viral-based expression systems may be utilized. In cases where an adenovirus is used as an expression vector, the NHP nucleotide sequence of interest may be ligated to an adenovirus transcription/translation control complex, e.g., the late promoter and tripartite leader sequence. This chimeric sequence may then be inserted in the adenovirus genome by in vitro or in vivo recombination. Insertion in a non-essential region of the viral genome (e.g., region El or E3) will result in a recombinant virus that is viable and capable of expressing a NHP product in infected hosts (e.g., See Logan & Shenk, 1984, Proc. Natl. Acad. Sci. USA 81:3655-3659). Specific initiation signals may also be required for efficient translation of inserted NHP nucleotide sequences. These signals include the ATG initiation codon and adjacent sequences. In cases where an entire NHP gene or cDNA, including its own initiation codon and adjacent sequences, is inserted into the appropriate expression vector, no additional translational control signals may be needed. However, in cases where only a portion of a NHP coding sequence is inserted, exogenous translational control signals, including, perhaps, the ATG initiation codon, must be provided. Furthermore, the initiation codon must be in phase with the reading frame of the desired coding sequence to ensure translation of the entire insert. These exogenous translational control signals and initiation codons can be of a variety of origins, both natural and synthetic. The efficiency of expression may be enhanced by the inclusion of appropriate transcription enhancer elements, transcription terminators, etc. (See Bitter et al., 1987, Methods in Enzymol. 153:516-544).

[0062] In addition, a host cell strain may be chosen that modulates the expression of the inserted sequences, or modifies and processes the expression product in the specific fashion desired. Such modifications ( e.g., glycosylation) and processing (e.g., cleavage) of protein products may be important for the function of the protein. Different host cells have characteristic and specific mechanisms for the post-translational processing and modification of proteins and expression products. Appropriate cell lines or host systems can be chosen to ensure the correct modification and processing of the foreign protein expressed. To this end, eukaryotic host cells which possess the cellular machinery for proper processing of the primary transcript, glycosylation, and phosphorylation of the expression product may be used. Such mammalian host cells include, but are not limited to, CHO, VERO, BHK, HeLa, COS, MDCK, 293, 3T3, WI38, and in particular, human cell lines.

[0063] For long-term, high-yield production of recombinant proteins, stable expression is preferred. For example, cell lines which stably express the NHP sequences described above can be engineered. Rather than using expression vectors which contain viral origins of replication, host cells can be transformed with DNA controlled by appropriate expression control elements (e.g., promoter, enhancer sequences, transcription terminators, polyadenylation sites, etc.), and a selectable marker. Following the introduction of the foreign DNA, engineered cells may be allowed to grow for 1-2 days in an enriched media, and then are switched to a selective media. The selectable marker in the recombinant plasmid confers resistance to the selection and allows cells to stably integrate the plasmid into their chromosomes and grow to form foci which in turn can be cloned and expanded into cell lines. This method may advantageously be used to engineer cell lines which express a NHP product. Such engineered cell lines may be particularly useful in screening and evaluation of compounds that affect the endogenous activity of a NHP product.

[0064] A number of selection systems may be used, including but not limited to the herpes simplex virus thymidine kinase (Wigler, et al., 1977, Cell 11:223), hypoxanthine-guanine phosphoribosyltransferase (Szybalska & Szybalski, 1962, Proc. Natl. Acad. Sci. USA 48:2026), and adenine phosphoribosyltransferase (Lowy, et al., 1980, Cell 22:817) genes, which can be employed in tk⁻, hgprt⁻ or aprt⁻ cells, respectively. Also, antimetabolite resistance can be used as the basis of selection for the following genes: dhfr, which confers resistance to methotrexate (Wigler, et al., 1980, Natl. Acad. Sci. USA 77:3567; O'Hare, et al., 1981, Proc. Natl. Acad. Sci. USA 78:1527); gpt, which confers resistance to mycophenolic acid (Mulligan & Berg, 1981, Proc. Natl. Acad. Sci. USA 78:2072); neo, which confers resistance to the aminoglycoside G-418 (Colberre-Garapin, et al., 1981, J. Mol. Biol. 150:1); and hygro, which confers resistance to hygromycin (Santerre, et al., 1984, Gene 30:147).

[0065] Alternatively, any fusion protein can be readily purified by utilizing an antibody specific for the fusion protein being expressed. For example, a system described by Janknecht et al. allows for the ready purification of non-denatured fusion proteins expressed in human cell lines (Janknecht, et al., 1991, Proc. Natl. Acad. Sci. USA 88:8972-8976). In this system, the sequence of interest is subcloned into a vaccinia recombination plasmid such that the sequence's open reading frame is translationally fused to an amino-terminal tag consisting of six histidine residues. Extracts from cells infected with recombinant vaccinia virus are loaded onto Ni²⁺nitriloacetic acid-agarose columns and histidine-tagged proteins are selectively eluted with imidazole-containing buffers.

[0066] Also encompassed by the present invention are fusion proteins that direct the NHP to a target organ and/or facilitate transport across the membrane into the cytosol. Conjugation of NHPs to antibody molecules or their Fab fragments could be used to target cells bearing a particular epitope. Attaching the appropriate signal sequence to the NHP would also transport the NHP to the desired location within the cell. Alternatively targeting of NHP or its nucleic acid sequence might be achieved using liposome or lipid complex based delivery systems. Such technologies are described in “Liposomes:A Practical Approach”, New, R. R. C., ed., Oxford University Press, New York and in U.S. Pat. Nos. 4,594,595, 5,459,127, 5,948,767 and 6,110,490 and their respective disclosures which are herein incorporated by reference in their entirety. Additionally embodied are novel protein constructs engineered in such a way that they facilitate transport of the NHP to the target site or desired organ, where they cross the cell membrane and/or the nucleus where the NHP can exert its functional activity. This goal may be achieved by coupling of the NHP to a cytokine or other ligand that provides targeting specificity, and/or to a protein transducing domain (see generally U.S. applications Ser. No. 60/111,701 and 60/056,713, both of which are herein incorporated by reference, for examples of such transducing sequences) to facilitate passage across cellular membranes and can optionally be engineered to include nuclear localization.

[0067] 5.3 Antibodies to NHP Products

[0068] Antibodies that specifically recognize one or more epitopes of a NHP, or epitopes of conserved variants of a NHP, or peptide fragments of a NHP are also encompassed by the invention. Such antibodies include but are not limited to polyclonal antibodies, monoclonal antibodies (mAbs), humanized or chimeric antibodies, single chain antibodies, Fab fragments, F(ab′)₂ fragments, fragments produced by a Fab expression library, anti-idiotypic (anti-Id) antibodies, and epitope-binding fragments of any of the above.

[0069] The antibodies of the invention may be used, for example, in the detection of a NHP in a biological sample and may, therefore, be utilized as part of a diagnostic or prognostic technique whereby patients may be tested for abnormal amounts of NHP. Such antibodies may also be utilized in conjunction with, for example, compound screening schemes for the evaluation of the effect of test compounds on expression and/or activity of a NHP expression product. Additionally, such antibodies can be used in conjunction gene therapy to, for example, evaluate the normal and/or engineered NHP-expressing cells prior to their introduction into the patient. Such antibodies may additionally be used as a method for the inhibition of abnormal NHP activity. Thus, such antibodies may, therefore, be utilized as part of treatment methods.

[0070] For the production of antibodies, various host animals may be immunized by injection with a NHP, an NHP peptide (e.g., one corresponding to a functional domain of a NHP), truncated NHP polypeptides (NHP in which one or more domains have been deleted), functional equivalents of a NHP or mutated variants of a NHP. Such host animals may include but are not limited to pigs, rabbits, mice, goats, and rats, to name but a few. Various adjuvants may be used to increase the immunological response, depending on the host species, including but not limited to Freund's adjuvant (complete and incomplete), mineral salts such as aluminum hydroxide or aluminum phosphate, chitosan, surface active substances such as lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, and potentially useful human adjuvants such as BCG (bacille Calmette-Guerin) and Corynebacterium parvum. Alternatively, the immune response could be enhanced by combination and or coupling with molecules such as keyhole limpet hemocyanin, tetanus toxoid, diphtheria toxoid, ovalbumin, cholera toxin or fragments thereof. Polyclonal antibodies are heterogeneous populations of antibody molecules derived from the sera of the immunized animals.

[0071] Monoclonal antibodies, which are homogeneous populations of antibodies to a particular antigen, can be obtained by any technique which provides for the production of antibody molecules by continuous cell lines in culture. These include, but are not limited to, the hybridoma technique of Kohler and Milstein, (1975, Nature 256:495-497; and U.S. Pat. No. 4,376,110), the human B-cell hybridoma technique (Kosbor et al., 1983, Immunology Today 4:72; Cole et al., 1983, Proc. Natl. Acad. Sci. USA 80:2026-2030), and the EBV-hybridoma technique (Cole et al., 1985, Monoclonal Antibodies And Cancer Therapy, Alan R. Liss, Inc., pp. 77-96). Such antibodies may be of any immunoglobulin class including IgG, IgM, IgE, IgA, IgD and any subclass thereof. The hybridoma producing the mAb of this invention may be cultivated in vitro or in vivo. Production of high titers of mabs in vivo makes this the presently preferred method of production.

[0072] In addition, techniques developed for the production of “chimeric antibodies” (Morrison et al., 1984, Proc. Natl. Acad. Sci., 81:6851-6855; Neuberger et al., 1984, Nature, 312:604-608; Takeda et al., 1985, Nature, 314:452-454) by splicing the genes from a mouse antibody molecule of appropriate antigen specificity together with genes from a human antibody molecule of appropriate biological activity can be used (see U.S. Pat. Nos. 5,877,397 and 6,075,181 herein incorporated by reference in their entirety). A chimeric antibody is a molecule in which different portions are derived from different animal species, such as those having a variable region derived from a murine mAb and a human immunoglobulin constant region. Such technologies are described in U.S. Pat. Nos. 6,075,181 and 5,877,397 and their respective disclosures which are herein incorporated by reference in their entirety. Also encompassed by the present invention is the use of fully humanized monoclonal antibodies as described in US Pat. No. 6,150,584 and respective disclosures which are herein incorporated by reference in their entirety.

[0073] Alternatively, techniques described for the production of single chain antibodies (U.S. Pat. No. 4,946,778; Bird, 1988, Science 242:423-426; Huston et al., 1988, Proc. Natl. Acad. Sci. USA 85:5879-5883; and Ward et al., 1989, Nature 341:544-546) can be adapted to produce single chain antibodies against NHP expression products. Single chain antibodies are formed by linking the heavy and light chain fragments of the Fv region via an amino acid bridge, resulting in a single chain polypeptide.

[0074] Antibody fragments which recognize specific epitopes may be generated by known techniques. For example, such fragments include, but are not limited to: the F(ab′)₂ fragments which can be produced by pepsin digestion of the antibody molecule and the Fab fragments which can be generated by reducing the disulfide bridges of the F(ab′)₂ fragments. Alternatively, Fab expression libraries may be constructed (Huse et al., 1989, Science, 246:1275-1281) to allow rapid and easy identification of monoclonal Fab fragments with the desired specificity.

[0075] Antibodies to a NHP can, in turn, be utilized to generate anti-idiotype antibodies that “mimic” a given NHP, using techniques well known to those skilled in the art. (See, e.g., Greenspan & Bona, 1993, FASEB J 7(5):437-444; and Nissinoff, 1991, J. Immunol. 147(8):2429-2438). For example antibodies which bind to a NHP domain and competitively inhibit the binding of NHP to its cognate receptor can be used to generate anti-idiotypes that “mimic” a NHP and, therefore, bind and activate or neutralize a receptor. Such anti-idiotypic antibodies or Fab fragments of such anti-idiotypes can be used in therapeutic regimens involving a NHP signaling pathway.

[0076] Additionally given the high degree of relatedness of mammalian NHPs, the presently described knock-out mice (having never seen NHP, and thus never been tolerized to NHP) have a unique utility, as they can be advantageously applied to the generation of antibodies against the disclosed mammalian NHP (i.e., NHP will be immunogenic in NHP knock-out animals).

[0077] The present invention is not to be limited in scope by the specific embodiments described herein, which are intended as single illustrations of individual aspects of the invention, and functionally equivalent methods and components are within the scope of the invention. Indeed, various modifications of the invention, in addition to those shown and described herein will become apparent to those skilled in the art from the foregoing description. Such modifications are intended to fall within the scope of the appended claims. All cited publications, patents, and patent applications are herein incorporated by reference in their entirety.

1 26 1 1356 DNA homo sapiens 1 atggctccac tccgcgcgct gctgtcctac ctgctgcctt tgcactgtgc gctctgcgcc 60 gccgcgggca gccggacccc agagctgcac ctctctggaa agctcagtga ctatggtgtg 120 acagtgccct gcagcacaga ctttcgggga cgcttcctct cccacgtggt gtctggccca 180 gcagcagcct ctgcagggag catggtagtg gacacgccac ccacactacc acgacactcc 240 agtcacctcc gggtggctcg cagccctctg cacccaggag ggaccctgtg gcctggcagg 300 gtggggcgcc actccctcta cttcaatgtc actgttttcg ggaaggaact gcacttgcgc 360 ctgcggccca atcggaggtt ggtagtgcca ggatcctcag tggagtggca ggaggatttt 420 cgggagctgt tccggcagcc cttacggcag gagtgtgtgt acactggagg tgtcactgga 480 atgcctgggg cagctgttgc catcagcaac tgtgacggat tggcgggcct catccgcaca 540 gacagcaccg acttcttcat tgagcctctg gagcggggcc agcaggagaa ggaggccagc 600 gggaggacac atgtggtgta ccgccgggag gccgtccagc aggagtgggc agaacctgac 660 ggggacctgc acaatgaagc ctttggcctg ggagaccttc ccaacctgct gggcctggtg 720 ggggaccagc tgggcgacac agagcggaag cggcggcatg ccaagccagg cagctacagc 780 atcgaggtgc tgctggtggt ggacgactcg gtggttcgct tccatggcaa ggagcatgtg 840 cagaactatg tcctcaccct catgaatatc gtagatgaga tttaccacga tgagtccctg 900 ggggttcata taaatattgc cctcgtccgc ttgatcatgg ttggctaccg acagtccctg 960 agcctgatcg agcgcgggaa cccctcacgc agcctggagc aggtgtgtcg ctgggcacac 1020 tcccagcagc gccaggaccc cagccacgct gagcaccatg accacgttgt gttcctcacc 1080 cggcaggact ttgggccctc agggtatgca cccgtcactg gcatgtgtca ccccctgagg 1140 agctgtgccc tcaaccatga ggatggcttc tcctcagcct tcgtgatagc tcatgagacc 1200 ggccacgtgc tcggcatgga gcatgacggt caggggaatg gctgtgcaga tgagaccagc 1260 ctgggcagcg tcatggcgcc cctggtgcag gctgccttcc accgcttcca ttggtcccgc 1320 tgcagcaagc tggagctcag ccgctacctc ccgtag 1356 2 451 PRT homo sapiens 2 Met Ala Pro Leu Arg Ala Leu Leu Ser Tyr Leu Leu Pro Leu His Cys 1 5 10 15 Ala Leu Cys Ala Ala Ala Gly Ser Arg Thr Pro Glu Leu His Leu Ser 20 25 30 Gly Lys Leu Ser Asp Tyr Gly Val Thr Val Pro Cys Ser Thr Asp Phe 35 40 45 Arg Gly Arg Phe Leu Ser His Val Val Ser Gly Pro Ala Ala Ala Ser 50 55 60 Ala Gly Ser Met Val Val Asp Thr Pro Pro Thr Leu Pro Arg His Ser 65 70 75 80 Ser His Leu Arg Val Ala Arg Ser Pro Leu His Pro Gly Gly Thr Leu 85 90 95 Trp Pro Gly Arg Val Gly Arg His Ser Leu Tyr Phe Asn Val Thr Val 100 105 110 Phe Gly Lys Glu Leu His Leu Arg Leu Arg Pro Asn Arg Arg Leu Val 115 120 125 Val Pro Gly Ser Ser Val Glu Trp Gln Glu Asp Phe Arg Glu Leu Phe 130 135 140 Arg Gln Pro Leu Arg Gln Glu Cys Val Tyr Thr Gly Gly Val Thr Gly 145 150 155 160 Met Pro Gly Ala Ala Val Ala Ile Ser Asn Cys Asp Gly Leu Ala Gly 165 170 175 Leu Ile Arg Thr Asp Ser Thr Asp Phe Phe Ile Glu Pro Leu Glu Arg 180 185 190 Gly Gln Gln Glu Lys Glu Ala Ser Gly Arg Thr His Val Val Tyr Arg 195 200 205 Arg Glu Ala Val Gln Gln Glu Trp Ala Glu Pro Asp Gly Asp Leu His 210 215 220 Asn Glu Ala Phe Gly Leu Gly Asp Leu Pro Asn Leu Leu Gly Leu Val 225 230 235 240 Gly Asp Gln Leu Gly Asp Thr Glu Arg Lys Arg Arg His Ala Lys Pro 245 250 255 Gly Ser Tyr Ser Ile Glu Val Leu Leu Val Val Asp Asp Ser Val Val 260 265 270 Arg Phe His Gly Lys Glu His Val Gln Asn Tyr Val Leu Thr Leu Met 275 280 285 Asn Ile Val Asp Glu Ile Tyr His Asp Glu Ser Leu Gly Val His Ile 290 295 300 Asn Ile Ala Leu Val Arg Leu Ile Met Val Gly Tyr Arg Gln Ser Leu 305 310 315 320 Ser Leu Ile Glu Arg Gly Asn Pro Ser Arg Ser Leu Glu Gln Val Cys 325 330 335 Arg Trp Ala His Ser Gln Gln Arg Gln Asp Pro Ser His Ala Glu His 340 345 350 His Asp His Val Val Phe Leu Thr Arg Gln Asp Phe Gly Pro Ser Gly 355 360 365 Tyr Ala Pro Val Thr Gly Met Cys His Pro Leu Arg Ser Cys Ala Leu 370 375 380 Asn His Glu Asp Gly Phe Ser Ser Ala Phe Val Ile Ala His Glu Thr 385 390 395 400 Gly His Val Leu Gly Met Glu His Asp Gly Gln Gly Asn Gly Cys Ala 405 410 415 Asp Glu Thr Ser Leu Gly Ser Val Met Ala Pro Leu Val Gln Ala Ala 420 425 430 Phe His Arg Phe His Trp Ser Arg Cys Ser Lys Leu Glu Leu Ser Arg 435 440 445 Tyr Leu Pro 450 3 894 DNA homo sapiens 3 atggctccac tccgcgcgct gctgtcctac ctgctgcctt tgcactgtgc gctctgcrcc 60 gccgcgggca gccggacccc agagctgcac ctctctggaa agctcagtga ctatggtgtg 120 acagtgccct gcagcacaga ctttcgggga cgcttcctct cccacgtggt gtctggccca 180 gcagcagcct ctgcagggag catggtagtg gacacgccac ccacactacc acgacactcc 240 agtcacctcc gggtggctcg cagccctctg cacccaggag ggaccctgtg gcctggcagg 300 gtggggcgcc actccctcta cttcaatgtc actgttttcg ggaaggaact gcacttgcgc 360 ctgcggccca atcggaggtt ggtagtgcca ggatcctcag tggagtggca ggaggatttt 420 cgggagctgt tccggcagcc cttacggcag gagtgtgtgt acactggagg tgtcactgga 480 atgcctgggg cagctgttgc catcagcaac tgtgacggat tggcgggcct catccgcaca 540 gacagcaccg acttcttcat tgagcctctg gagcggggcc agcaggagaa ggaggccagc 600 gggaggacac atgtggtgta ccgccgggag gccgtccagc aggagtgggc agaacctgac 660 ggggacctgc acaatgaagc ctttggcctg ggagaccttc ccaacctgct gggcctggtg 720 ggggaccagc tgggcgacac agagcggaag cggcggcatg ccaagccagg cagctacagc 780 atcgaggtgc tgctggtggt ggacgactcg gtggttcgct tccatggcaa ggagcatgtg 840 cagaactatg tcctcaccct catgaatatc gtgtgcttac agggaagtcc ataa 894 4 297 PRT homo sapiens 4 Met Ala Pro Leu Arg Ala Leu Leu Ser Tyr Leu Leu Pro Leu His Cys 1 5 10 15 Ala Leu Cys Thr Ala Ala Gly Ser Arg Thr Pro Glu Leu His Leu Ser 20 25 30 Gly Lys Leu Ser Asp Tyr Gly Val Thr Val Pro Cys Ser Thr Asp Phe 35 40 45 Arg Gly Arg Phe Leu Ser His Val Val Ser Gly Pro Ala Ala Ala Ser 50 55 60 Ala Gly Ser Met Val Val Asp Thr Pro Pro Thr Leu Pro Arg His Ser 65 70 75 80 Ser His Leu Arg Val Ala Arg Ser Pro Leu His Pro Gly Gly Thr Leu 85 90 95 Trp Pro Gly Arg Val Gly Arg His Ser Leu Tyr Phe Asn Val Thr Val 100 105 110 Phe Gly Lys Glu Leu His Leu Arg Leu Arg Pro Asn Arg Arg Leu Val 115 120 125 Val Pro Gly Ser Ser Val Glu Trp Gln Glu Asp Phe Arg Glu Leu Phe 130 135 140 Arg Gln Pro Leu Arg Gln Glu Cys Val Tyr Thr Gly Gly Val Thr Gly 145 150 155 160 Met Pro Gly Ala Ala Val Ala Ile Ser Asn Cys Asp Gly Leu Ala Gly 165 170 175 Leu Ile Arg Thr Asp Ser Thr Asp Phe Phe Ile Glu Pro Leu Glu Arg 180 185 190 Gly Gln Gln Glu Lys Glu Ala Ser Gly Arg Thr His Val Val Tyr Arg 195 200 205 Arg Glu Ala Val Gln Gln Glu Trp Ala Glu Pro Asp Gly Asp Leu His 210 215 220 Asn Glu Ala Phe Gly Leu Gly Asp Leu Pro Asn Leu Leu Gly Leu Val 225 230 235 240 Gly Asp Gln Leu Gly Asp Thr Glu Arg Lys Arg Arg His Ala Lys Pro 245 250 255 Gly Ser Tyr Ser Ile Glu Val Leu Leu Val Val Asp Asp Ser Val Val 260 265 270 Arg Phe His Gly Lys Glu His Val Gln Asn Tyr Val Leu Thr Leu Met 275 280 285 Asn Ile Val Cys Leu Gln Gly Ser Pro 290 295 5 1461 DNA homo sapiens 5 atggctccac tccgcgcgct gctgtcctac ctgctgcctt tgcactgtgc gctctgcrcc 60 gccgcgggca gccggacccc agagctgcac ctctctggaa agctcagtga ctatggtgtg 120 acagtgccct gcagcacaga ctttcgggga cgcttcctct cccacgtggt gtctggccca 180 gcagcagcct ctgcagggag catggtagtg gacacgccac ccacactacc acgacactcc 240 agtcacctcc gggtggctcg cagccctctg cacccaggag ggaccctgtg gcctggcagg 300 gtggggcgcc actccctcta cttcaatgtc actgttttcg ggaaggaact gcacttgcgc 360 ctgcggccca atcggaggtt ggtagtgcca ggatcctcag tggagtggca ggaggatttt 420 cgggagctgt tccggcagcc cttacggcag gagtgtgtgt acactggagg tgtcactgga 480 atgcctgggg cagctgttgc catcagcaac tgtgacggat tggcgggcct catccgcaca 540 gacagcaccg acttcttcat tgagcctctg gagcggggcc agcaggagaa ggaggccagc 600 gggaggacac atgtggtgta ccgccgggag gccgtccagc aggagtgggc agaacctgac 660 ggggacctgc acaatgaagc ctttggcctg ggagaccttc ccaacctgct gggcctggtg 720 ggggaccagc tgggcgacac agagcggaag cggcggcatg ccaagccagg cagctacagc 780 atcgaggtgc tgctggtggt ggacgactcg gtggttcgct tccatggcaa ggagcatgtg 840 cagaactatg tcctcaccct catgaatatc gtagatgaga tttaccacga tgagtccctg 900 ggggttcata taaatattgc cctcgtccgc ttgatcatgg ttggctaccg acagtccctg 960 agcctgatcg agcgcgggaa cccctcacgc agcctggagc aggtgtgtcg ctgggcacac 1020 tcccagcagc gccaggaccc cagccacgct gagcaccatg accacgttgt gttcctcacc 1080 cggcaggact ttgggccctc agggtatgca cccgtcactg gcatgtgtca ccccctgagg 1140 agctgtgccc tcaaccatga ggatggcttc tcctcagcct tcgtgatagc tcatgagacc 1200 ggccacgtgc tcggcatgga gcatgacggt caggggaatg gctgtgcaga tgagaccagc 1260 ctgggcagcg tcatggcgcc cctggtgcag gctgccttcc accgcttcca ttggtcccgc 1320 tgcagcaagc tggagctcag ccgctacctc ccctcctacg actgcctcct cgatgacccc 1380 tttgatcctg ccacctgccc gggcggccgc tcgagcccta tagtgagtcg tattaggatg 1440 gccgccactc cctttactta a 1461 6 486 PRT homo sapiens 6 Met Ala Pro Leu Arg Ala Leu Leu Ser Tyr Leu Leu Pro Leu His Cys 1 5 10 15 Ala Leu Cys Thr Ala Ala Gly Ser Arg Thr Pro Glu Leu His Leu Ser 20 25 30 Gly Lys Leu Ser Asp Tyr Gly Val Thr Val Pro Cys Ser Thr Asp Phe 35 40 45 Arg Gly Arg Phe Leu Ser His Val Val Ser Gly Pro Ala Ala Ala Ser 50 55 60 Ala Gly Ser Met Val Val Asp Thr Pro Pro Thr Leu Pro Arg His Ser 65 70 75 80 Ser His Leu Arg Val Ala Arg Ser Pro Leu His Pro Gly Gly Thr Leu 85 90 95 Trp Pro Gly Arg Val Gly Arg His Ser Leu Tyr Phe Asn Val Thr Val 100 105 110 Phe Gly Lys Glu Leu His Leu Arg Leu Arg Pro Asn Arg Arg Leu Val 115 120 125 Val Pro Gly Ser Ser Val Glu Trp Gln Glu Asp Phe Arg Glu Leu Phe 130 135 140 Arg Gln Pro Leu Arg Gln Glu Cys Val Tyr Thr Gly Gly Val Thr Gly 145 150 155 160 Met Pro Gly Ala Ala Val Ala Ile Ser Asn Cys Asp Gly Leu Ala Gly 165 170 175 Leu Ile Arg Thr Asp Ser Thr Asp Phe Phe Ile Glu Pro Leu Glu Arg 180 185 190 Gly Gln Gln Glu Lys Glu Ala Ser Gly Arg Thr His Val Val Tyr Arg 195 200 205 Arg Glu Ala Val Gln Gln Glu Trp Ala Glu Pro Asp Gly Asp Leu His 210 215 220 Asn Glu Ala Phe Gly Leu Gly Asp Leu Pro Asn Leu Leu Gly Leu Val 225 230 235 240 Gly Asp Gln Leu Gly Asp Thr Glu Arg Lys Arg Arg His Ala Lys Pro 245 250 255 Gly Ser Tyr Ser Ile Glu Val Leu Leu Val Val Asp Asp Ser Val Val 260 265 270 Arg Phe His Gly Lys Glu His Val Gln Asn Tyr Val Leu Thr Leu Met 275 280 285 Asn Ile Val Asp Glu Ile Tyr His Asp Glu Ser Leu Gly Val His Ile 290 295 300 Asn Ile Ala Leu Val Arg Leu Ile Met Val Gly Tyr Arg Gln Ser Leu 305 310 315 320 Ser Leu Ile Glu Arg Gly Asn Pro Ser Arg Ser Leu Glu Gln Val Cys 325 330 335 Arg Trp Ala His Ser Gln Gln Arg Gln Asp Pro Ser His Ala Glu His 340 345 350 His Asp His Val Val Phe Leu Thr Arg Gln Asp Phe Gly Pro Ser Gly 355 360 365 Tyr Ala Pro Val Thr Gly Met Cys His Pro Leu Arg Ser Cys Ala Leu 370 375 380 Asn His Glu Asp Gly Phe Ser Ser Ala Phe Val Ile Ala His Glu Thr 385 390 395 400 Gly His Val Leu Gly Met Glu His Asp Gly Gln Gly Asn Gly Cys Ala 405 410 415 Asp Glu Thr Ser Leu Gly Ser Val Met Ala Pro Leu Val Gln Ala Ala 420 425 430 Phe His Arg Phe His Trp Ser Arg Cys Ser Lys Leu Glu Leu Ser Arg 435 440 445 Tyr Leu Pro Ser Tyr Asp Cys Leu Leu Asp Asp Pro Phe Asp Pro Ala 450 455 460 Thr Cys Pro Gly Gly Arg Ser Ser Pro Ile Val Ser Arg Ile Arg Met 465 470 475 480 Ala Ala Thr Pro Phe Thr 485 7 3669 DNA homo sapiens 7 atggctccac tccgcgcgct gctgtcctac ctgctgcctt tgcactgtgc gctctgcrcc 60 gccgcgggca gccggacccc agagctgcac ctctctggaa agctcagtga ctatggtgtg 120 acagtgccct gcagcacaga ctttcgggga cgcttcctct cccacgtggt gtctggccca 180 gcagcagcct ctgcagggag catggtagtg gacacgccac ccacactacc acgacactcc 240 agtcacctcc gggtggctcg cagccctctg cacccaggag ggaccctgtg gcctggcagg 300 gtggggcgcc actccctcta cttcaatgtc actgttttcg ggaaggaact gcacttgcgc 360 ctgcggccca atcggaggtt ggtagtgcca ggatcctcag tggagtggca ggaggatttt 420 cgggagctgt tccggcagcc cttacggcag gagtgtgtgt acactggagg tgtcactgga 480 atgcctgggg cagctgttgc catcagcaac tgtgacggat tggcgggcct catccgcaca 540 gacagcaccg acttcttcat tgagcctctg gagcggggcc agcaggagaa ggaggccagc 600 gggaggacac atgtggtgta ccgccgggag gccgtccagc aggagtgggc agaacctgac 660 ggggacctgc acaatgaagc ctttggcctg ggagaccttc ccaacctgct gggcctggtg 720 ggggaccagc tgggcgacac agagcggaag cggcggcatg ccaagccagg cagctacagc 780 atcgaggtgc tgctggtggt ggacgactcg gtggttcgct tccatggcaa ggagcatgtg 840 cagaactatg tcctcaccct catgaatatc gtagatgaga tttaccacga tgagtccctg 900 ggggttcata taaatattgc cctcgtccgc ttgatcatgg ttggctaccg acagtccctg 960 agcctgatcg agcgcgggaa cccctcacgc agcctggagc aggtgtgtcg ctgggcacac 1020 tcccagcagc gccaggaccc cagccacgct gagcaccatg accacgttgt gttcctcacc 1080 cggcaggact ttgggccctc agggtatgca cccgtcactg gcatgtgtca ccccctgagg 1140 agctgtgccc tcaaccatga ggatggcttc tcctcagcct tcgtgatagc tcatgagacc 1200 ggccacgtgc tcggcatgga gcatgacggt caggggaatg gctgtgcaga tgagaccagc 1260 ctgggcagcg tcatggcgcc cctggtgcag gctgccttcc accgcttcca ttggtcccgc 1320 tgcagcaagc tggagctcag ccgctacctc ccctcctacg actgcctcct cgatgacccc 1380 tttgatcctg cctggcccca gcccccagag ctgcctggga tcaactactc aatggatgag 1440 cagtgccgct ttgactttgg cagtggctac cagacctgct tggcattcag gacctttgag 1500 ccctgcaagc agctgtggtg cagccatcct gacaaccmgt ayttctgcaa gaccaagaag 1560 gggcccccgc tggatgggac tgagtgtgca cccggcaagt ggtgcttcaa aggtcactgc 1620 atctggaagt cgccggagca gacatatggc caggatggag gctggagctc ctggaccaag 1680 tttgggtcat gttcgcggtc atgtgggggc ggggtgcgat cccgcagccg gagctgcaac 1740 aacccctccc cagcctatgg aggccgccyg tgcttagggc ccatgttcga gtaccaggtc 1800 tgcaacagcg aggagtgccc tgggacctac gaggacttcc gggcccagca gtgtgccaag 1860 cgcaactcst actatgtgca ccagaatgcc aagcacagst gggtgcccta cgagcctgac 1920 gatgacgccc agaagtgtga gctgatctgc cagtcggcgg acacrgggga cgtggtgttc 1980 atgaaccagg tggttcacga tgggacacgc tgcagctacc gggacccata cagcgtctgt 2040 gcgcgtggcg agtgtgtgcc tgtcggctgt gacaaggagg tggggtccat gaaggcggat 2100 gacaagtgtg gagtctgcgg gggtgacaac tcccactgca ggactgtgaa ggggacgctg 2160 ggcaaggcct ccaagcaggc aggagctctc aagctggtgc agatcccagc aggtgccagg 2220 cacatccaga ttgaggcact ggagaagtcc ccccaccgsw ywgtggtgaa gaaccaggtc 2280 accggcagct tcatcctcaa ccccaagggc aaggaagcca caagccggac cttcaccgcc 2340 atgggcctgg agtgggagga tgcggtggag gatgccaagg aaagcctcaa gaccagcggg 2400 cccctgcctg aagccattgc catcctggct ctccccccaa ctgagggtgg cccccgcagc 2460 agcctggcct acaagtacgt catccatgag gacctgctgc cccttatcgg gagcaacaat 2520 gtgctcctgg aggagatgga cacctatgag tgggcgctca agagctgggc cccctgcagc 2580 aaggcctgtg gaggagggat ccagttcacc aaatacggct gccggcgcag acgagaccac 2640 cacatggtgc agcgacacct gtgtgaccac aagaagaggc ccaagcccat ccgccggcgc 2700 tgcaaccagc acccgtgctc tcagcctgtg tgggtgacgg aggagtgggg tgcctgcagc 2760 cggagctgtg ggaagctggg ggtgcagaca cgggggatac agtgcctgct gcccctctcc 2820 aatggaaccc acaaggtcat gccggccaaa gcctgcgccg gggaccggcc tgaggcccga 2880 cggccctgtc tccgagtgcc ctgcccagcc cagtggaggc tgggagcctg gtcccagtgc 2940 tctgccacct gtggagaggg catccagcag cggcaggtgg tgtgcaggac caacgccaac 3000 agcctcgggc attgcgaggg ggataggcca gacactgtcc aggtctgcar cctgcccgcc 3060 tgtggaggaa atcaccagaa ctccacggtg agggccgatg tctgggaact tgggacgcca 3120 gaggggcagt gggtgccaca atctgraccc ctacatccca ttaacaagat atcatcaatg 3180 tgtgcagcgg agccctgcac gggagacagg tctgtcttct gccagatgga agtgctcgat 3240 cgctactgct ccattcccgg ctaccaccgg ctctgctgtg tgtcctgcat caagaaggcc 3300 tcgggcccca accctggccc agaccctggc ccaacctcac tgcccccctt ctccactcct 3360 ggaagcccct taccaggacc ccaggaccct gcagatgctg cagagcctcc tggaaagcca 3420 acgggatcag aggaccatca gcatggccga gccacacagc tcccaggagc tctggataca 3480 agctccccag ggacccagca tccctttgcc cctgagacac caatccctgg agcatcctgg 3540 agcatctccc ctaccacccc cggggggctg ccttggggct ggactcagac acctacgcca 3600 gtccctgagg acaaagggca acctggagaa gacctgagac ctgcccgggc ggccgctcga 3660 gccctatag 3669 8 1222 PRT homo sapiens 8 Met Ala Pro Leu Arg Ala Leu Leu Ser Tyr Leu Leu Pro Leu His Cys 1 5 10 15 Ala Leu Cys Thr Ala Ala Gly Ser Arg Thr Pro Glu Leu His Leu Ser 20 25 30 Gly Lys Leu Ser Asp Tyr Gly Val Thr Val Pro Cys Ser Thr Asp Phe 35 40 45 Arg Gly Arg Phe Leu Ser His Val Val Ser Gly Pro Ala Ala Ala Ser 50 55 60 Ala Gly Ser Met Val Val Asp Thr Pro Pro Thr Leu Pro Arg His Ser 65 70 75 80 Ser His Leu Arg Val Ala Arg Ser Pro Leu His Pro Gly Gly Thr Leu 85 90 95 Trp Pro Gly Arg Val Gly Arg His Ser Leu Tyr Phe Asn Val Thr Val 100 105 110 Phe Gly Lys Glu Leu His Leu Arg Leu Arg Pro Asn Arg Arg Leu Val 115 120 125 Val Pro Gly Ser Ser Val Glu Trp Gln Glu Asp Phe Arg Glu Leu Phe 130 135 140 Arg Gln Pro Leu Arg Gln Glu Cys Val Tyr Thr Gly Gly Val Thr Gly 145 150 155 160 Met Pro Gly Ala Ala Val Ala Ile Ser Asn Cys Asp Gly Leu Ala Gly 165 170 175 Leu Ile Arg Thr Asp Ser Thr Asp Phe Phe Ile Glu Pro Leu Glu Arg 180 185 190 Gly Gln Gln Glu Lys Glu Ala Ser Gly Arg Thr His Val Val Tyr Arg 195 200 205 Arg Glu Ala Val Gln Gln Glu Trp Ala Glu Pro Asp Gly Asp Leu His 210 215 220 Asn Glu Ala Phe Gly Leu Gly Asp Leu Pro Asn Leu Leu Gly Leu Val 225 230 235 240 Gly Asp Gln Leu Gly Asp Thr Glu Arg Lys Arg Arg His Ala Lys Pro 245 250 255 Gly Ser Tyr Ser Ile Glu Val Leu Leu Val Val Asp Asp Ser Val Val 260 265 270 Arg Phe His Gly Lys Glu His Val Gln Asn Tyr Val Leu Thr Leu Met 275 280 285 Asn Ile Val Asp Glu Ile Tyr His Asp Glu Ser Leu Gly Val His Ile 290 295 300 Asn Ile Ala Leu Val Arg Leu Ile Met Val Gly Tyr Arg Gln Ser Leu 305 310 315 320 Ser Leu Ile Glu Arg Gly Asn Pro Ser Arg Ser Leu Glu Gln Val Cys 325 330 335 Arg Trp Ala His Ser Gln Gln Arg Gln Asp Pro Ser His Ala Glu His 340 345 350 His Asp His Val Val Phe Leu Thr Arg Gln Asp Phe Gly Pro Ser Gly 355 360 365 Tyr Ala Pro Val Thr Gly Met Cys His Pro Leu Arg Ser Cys Ala Leu 370 375 380 Asn His Glu Asp Gly Phe Ser Ser Ala Phe Val Ile Ala His Glu Thr 385 390 395 400 Gly His Val Leu Gly Met Glu His Asp Gly Gln Gly Asn Gly Cys Ala 405 410 415 Asp Glu Thr Ser Leu Gly Ser Val Met Ala Pro Leu Val Gln Ala Ala 420 425 430 Phe His Arg Phe His Trp Ser Arg Cys Ser Lys Leu Glu Leu Ser Arg 435 440 445 Tyr Leu Pro Ser Tyr Asp Cys Leu Leu Asp Asp Pro Phe Asp Pro Ala 450 455 460 Trp Pro Gln Pro Pro Glu Leu Pro Gly Ile Asn Tyr Ser Met Asp Glu 465 470 475 480 Gln Cys Arg Phe Asp Phe Gly Ser Gly Tyr Gln Thr Cys Leu Ala Phe 485 490 495 Arg Thr Phe Glu Pro Cys Lys Gln Leu Trp Cys Ser His Pro Asp Asn 500 505 510 Pro Tyr Phe Cys Lys Thr Lys Lys Gly Pro Pro Leu Asp Gly Thr Glu 515 520 525 Cys Ala Pro Gly Lys Trp Cys Phe Lys Gly His Cys Ile Trp Lys Ser 530 535 540 Pro Glu Gln Thr Tyr Gly Gln Asp Gly Gly Trp Ser Ser Trp Thr Lys 545 550 555 560 Phe Gly Ser Cys Ser Arg Ser Cys Gly Gly Gly Val Arg Ser Arg Ser 565 570 575 Arg Ser Cys Asn Asn Pro Ser Pro Ala Tyr Gly Gly Arg Pro Cys Leu 580 585 590 Gly Pro Met Phe Glu Tyr Gln Val Cys Asn Ser Glu Glu Cys Pro Gly 595 600 605 Thr Tyr Glu Asp Phe Arg Ala Gln Gln Cys Ala Lys Arg Asn Ser Tyr 610 615 620 Tyr Val His Gln Asn Ala Lys His Ser Trp Val Pro Tyr Glu Pro Asp 625 630 635 640 Asp Asp Ala Gln Lys Cys Glu Leu Ile Cys Gln Ser Ala Asp Thr Gly 645 650 655 Asp Val Val Phe Met Asn Gln Val Val His Asp Gly Thr Arg Cys Ser 660 665 670 Tyr Arg Asp Pro Tyr Ser Val Cys Ala Arg Gly Glu Cys Val Pro Val 675 680 685 Gly Cys Asp Lys Glu Val Gly Ser Met Lys Ala Asp Asp Lys Cys Gly 690 695 700 Val Cys Gly Gly Asp Asn Ser His Cys Arg Thr Val Lys Gly Thr Leu 705 710 715 720 Gly Lys Ala Ser Lys Gln Ala Gly Ala Leu Lys Leu Val Gln Ile Pro 725 730 735 Ala Gly Ala Arg His Ile Gln Ile Glu Ala Leu Glu Lys Ser Pro His 740 745 750 Arg Ser Val Val Lys Asn Gln Val Thr Gly Ser Phe Ile Leu Asn Pro 755 760 765 Lys Gly Lys Glu Ala Thr Ser Arg Thr Phe Thr Ala Met Gly Leu Glu 770 775 780 Trp Glu Asp Ala Val Glu Asp Ala Lys Glu Ser Leu Lys Thr Ser Gly 785 790 795 800 Pro Leu Pro Glu Ala Ile Ala Ile Leu Ala Leu Pro Pro Thr Glu Gly 805 810 815 Gly Pro Arg Ser Ser Leu Ala Tyr Lys Tyr Val Ile His Glu Asp Leu 820 825 830 Leu Pro Leu Ile Gly Ser Asn Asn Val Leu Leu Glu Glu Met Asp Thr 835 840 845 Tyr Glu Trp Ala Leu Lys Ser Trp Ala Pro Cys Ser Lys Ala Cys Gly 850 855 860 Gly Gly Ile Gln Phe Thr Lys Tyr Gly Cys Arg Arg Arg Arg Asp His 865 870 875 880 His Met Val Gln Arg His Leu Cys Asp His Lys Lys Arg Pro Lys Pro 885 890 895 Ile Arg Arg Arg Cys Asn Gln His Pro Cys Ser Gln Pro Val Trp Val 900 905 910 Thr Glu Glu Trp Gly Ala Cys Ser Arg Ser Cys Gly Lys Leu Gly Val 915 920 925 Gln Thr Arg Gly Ile Gln Cys Leu Leu Pro Leu Ser Asn Gly Thr His 930 935 940 Lys Val Met Pro Ala Lys Ala Cys Ala Gly Asp Arg Pro Glu Ala Arg 945 950 955 960 Arg Pro Cys Leu Arg Val Pro Cys Pro Ala Gln Trp Arg Leu Gly Ala 965 970 975 Trp Ser Gln Cys Ser Ala Thr Cys Gly Glu Gly Ile Gln Gln Arg Gln 980 985 990 Val Val Cys Arg Thr Asn Ala Asn Ser Leu Gly His Cys Glu Gly Asp 995 1000 1005 Arg Pro Asp Thr Val Gln Val Cys Ser Leu Pro Ala Cys Gly Gly Asn 1010 1015 1020 His Gln Asn Ser Thr Val Arg Ala Asp Val Trp Glu Leu Gly Thr Pro 1025 1030 1035 1040 Glu Gly Gln Trp Val Pro Gln Ser Gly Pro Leu His Pro Ile Asn Lys 1045 1050 1055 Ile Ser Ser Met Cys Ala Ala Glu Pro Cys Thr Gly Asp Arg Ser Val 1060 1065 1070 Phe Cys Gln Met Glu Val Leu Asp Arg Tyr Cys Ser Ile Pro Gly Tyr 1075 1080 1085 His Arg Leu Cys Cys Val Ser Cys Ile Lys Lys Ala Ser Gly Pro Asn 1090 1095 1100 Pro Gly Pro Asp Pro Gly Pro Thr Ser Leu Pro Pro Phe Ser Thr Pro 1105 1110 1115 1120 Gly Ser Pro Leu Pro Gly Pro Gln Asp Pro Ala Asp Ala Ala Glu Pro 1125 1130 1135 Pro Gly Lys Pro Thr Gly Ser Glu Asp His Gln His Gly Arg Ala Thr 1140 1145 1150 Gln Leu Pro Gly Ala Leu Asp Thr Ser Ser Pro Gly Thr Gln His Pro 1155 1160 1165 Phe Ala Pro Glu Thr Pro Ile Pro Gly Ala Ser Trp Ser Ile Ser Pro 1170 1175 1180 Thr Thr Pro Gly Gly Leu Pro Trp Gly Trp Thr Gln Thr Pro Thr Pro 1185 1190 1195 1200 Val Pro Glu Asp Lys Gly Gln Pro Gly Glu Asp Leu Arg Pro Ala Arg 1205 1210 1215 Ala Ala Ala Arg Ala Leu 1220 9 3660 DNA homo sapiens 9 atggctccac tccgcgcgct gctgtcctac ctgctgcctt tgcactgtgc gctctgcrcc 60 gccgcgggca gccggacccc agagctgcac ctctctggaa agctcagtga ctatggtgtg 120 acagtgccct gcagcacaga ctttcgggga cgcttcctct cccacgtggt gtctggccca 180 gcagcagcct ctgcagggag catggtagtg gacacgccac ccacactacc acgacactcc 240 agtcacctcc gggtggctcg cagccctctg cacccaggag ggaccctgtg gcctggcagg 300 gtggggcgcc actccctcta cttcaatgtc actgttttcg ggaaggaact gcacttgcgc 360 ctgcggccca atcggaggtt ggtagtgcca ggatcctcag tggagtggca ggaggatttt 420 cgggagctgt tccggcagcc cttacggcag gagtgtgtgt acactggagg tgtcactgga 480 atgcctgggg cagctgttgc catcagcaac tgtgacggat tggcgggcct catccgcaca 540 gacagcaccg acttcttcat tgagcctctg gagcggggcc agcaggagaa ggaggccagc 600 gggaggacac atgtggtgta ccgccgggag gccgtccagc aggagtgggc agaacctgac 660 ggggacctgc acaatgaagc ctttggcctg ggagaccttc ccaacctgct gggcctggtg 720 ggggaccagc tgggcgacac agagcggaag cggcggcatg ccaagccagg cagctacagc 780 atcgaggtgc tgctggtggt ggacgactcg gtggttcgct tccatggcaa ggagcatgtg 840 cagaactatg tcctcaccct catgaatatc gtagatgaga tttaccacga tgagtccctg 900 ggggttcata taaatattgc cctcgtccgc ttgatcatgg ttggctaccg acagtccctg 960 agcctgatcg agcgcgggaa cccctcacgc agcctggagc aggtgtgtcg ctgggcacac 1020 tcccagcagc gccaggaccc cagccacgct gagcaccatg accacgttgt gttcctcacc 1080 cggcaggact ttgggccctc agggtatgca cccswywctg gcatgtgtca ccccctgagg 1140 agctgtgccc tcaaccatga ggatggcttc tcctcagcct tcgtgatagc tcatgagacc 1200 ggccacgtgc tcggcatgga gcatgacggt caggggaatg gctgtgcaga tgagaccagc 1260 ctgggcagcg tcatggcgcc cctggtgcag gctgccttcc accgcttcca ttggtcccgc 1320 tgcagcaagc tggagctcag ccgctacctc ccctcctacg actgcctcct cgatgacccc 1380 tttgatcctg cctggcccca gcccccagag ctgcctggga tcaactactc aatggatgag 1440 cagtgccgct ttgactttgg cagtggctac cagacctgct tggcattcag gacctttgag 1500 ccctgcaagc agctgtggtg cagccatcct gacaaccmgt ayttctgcaa gaccaagaag 1560 gggcccccgc tggatgggac tgagtgtgca cccggcaagt ggtgcttcaa aggtcactgc 1620 atctggaagt cgccggagca gacatatggc caggatggag gctggagctc ctggaccaag 1680 tttgggtcat gttcgcggtc atgtgggggc ggggtgcgat cccgcagccg gagctgcaac 1740 aacccctccc cagcctatgg aggccgccyg tgcttagggc ccatgttcga gtaccaggtc 1800 tgcaacagcg aggagtgccc tgggacctac gaggacttcc gggcccagca gtgtgccaag 1860 cgcaactcst actatgtgca ccagaatgcc aagcacagst gggtgcccta cgagcctgac 1920 gatgacgccc agaagtgtga gctgatctgc cagtcggcgg acacrgggga cgtggtgttc 1980 atgaaccagg tggttcacga tgggacacgc tgcagctacc gggacccata cagcgtctgt 2040 gcgcgtggcg agtgtgtgcc tgtcggctgt gacaaggagg tggggtccat gaaggcggat 2100 gacaagtgtg gagtctgcgg gggtgacaac tcccactgca ggactgtgaa ggggacgctg 2160 ggcaaggcct ccaagcaggc aggagctctc aagctggtgc agatcccagc aggtgccagg 2220 cacatccaga ttgaggcact ggagaagtcc ccccaccgsw ywgtggtgaa gaaccaggtc 2280 accggcagct tcatcctcaa ccccaagggc aaggaagcca caagccggac cttcaccgcc 2340 atgggcctgg agtgggagga tgcggtggag gatgccaagg aaagcctcaa gaccagcggg 2400 cccctgcctg aagccattgc catcctggct ctccccccaa ctgagggtgg cccccgcagc 2460 agcctggcct acaagtacgt catccatgag gacctgctgc cccttatcgg gagcaacaat 2520 gtgctcctgg aggagatgga cacctatgag tgggcgctca agagctgggc cccctgcagc 2580 aaggcctgtg gaggagggat ccagttcacc aaatacggct gccggcgcag acgagaccac 2640 cacatggtgc agcgacacct gtgtgaccac aagaagaggc ccaagcccat ccgccggcgc 2700 tgcaaccagc acccgtgctc tcagcctgtg tgggtgacgg aggagtgggg tgcctgcagc 2760 cggagctgtg ggaagctggg ggtgcagaca cgggggatac agtgcctgct gcccctctcc 2820 aatggaaccc acaaggtcat gccggccaaa gcctgcgccg gggaccggcc tgaggcccga 2880 cggccctgtc tccgagtgcc ctgcccagcc cagtggaggc tgggagcctg gtcccagtgc 2940 tctgccacct gtggagaggg catccagcag cggcaggtgg tgtgcaggac caacgccaac 3000 agcctcgggc attgcgaggg ggataggcca gacactgtcc aggtctgcar cctgcccgcc 3060 tgtggaggaa atcaccagaa ctccacggtg agggccgatg tctgggaact tgggacgcca 3120 gaggggcagt gggtgccaca atctgraccc ctacatccca ttaacaagat atcatcaacg 3180 gagccctgca cgggagacag gtctgtcttc tgccagatgg aagtgctcga tcgctactgc 3240 tccattcccg gctaccaccg gctctgctgt gtgtcctgca tcaagaaggc ctcgggcccc 3300 aaccctggcc cagaccctgg cccaacctca ctgcccccct tctccactcc tggaagcccc 3360 ttaccaggac cccaggaccc tgcagatgct gcagagcctc ctggaaagcc aacgggatca 3420 gaggaccatc agcatggccg agccacacag ctcccaggag ctctggatac aagctcccca 3480 gggacccagc atccctttgc ccctgagaca ccaatccctg gagcatcctg gagcatctcc 3540 cctaccaccc ccggggggct gccttggggc tggactcaga cacctacgcc agtccctgag 3600 gacaaagggc aacctggaga agacctgaga cctgcccggg cggccgctcg agccctatag 3660 10 1219 PRT homo sapiens 10 Met Ala Pro Leu Arg Ala Leu Leu Ser Tyr Leu Leu Pro Leu His Cys 1 5 10 15 Ala Leu Cys Thr Ala Ala Gly Ser Arg Thr Pro Glu Leu His Leu Ser 20 25 30 Gly Lys Leu Ser Asp Tyr Gly Val Thr Val Pro Cys Ser Thr Asp Phe 35 40 45 Arg Gly Arg Phe Leu Ser His Val Val Ser Gly Pro Ala Ala Ala Ser 50 55 60 Ala Gly Ser Met Val Val Asp Thr Pro Pro Thr Leu Pro Arg His Ser 65 70 75 80 Ser His Leu Arg Val Ala Arg Ser Pro Leu His Pro Gly Gly Thr Leu 85 90 95 Trp Pro Gly Arg Val Gly Arg His Ser Leu Tyr Phe Asn Val Thr Val 100 105 110 Phe Gly Lys Glu Leu His Leu Arg Leu Arg Pro Asn Arg Arg Leu Val 115 120 125 Val Pro Gly Ser Ser Val Glu Trp Gln Glu Asp Phe Arg Glu Leu Phe 130 135 140 Arg Gln Pro Leu Arg Gln Glu Cys Val Tyr Thr Gly Gly Val Thr Gly 145 150 155 160 Met Pro Gly Ala Ala Val Ala Ile Ser Asn Cys Asp Gly Leu Ala Gly 165 170 175 Leu Ile Arg Thr Asp Ser Thr Asp Phe Phe Ile Glu Pro Leu Glu Arg 180 185 190 Gly Gln Gln Glu Lys Glu Ala Ser Gly Arg Thr His Val Val Tyr Arg 195 200 205 Arg Glu Ala Val Gln Gln Glu Trp Ala Glu Pro Asp Gly Asp Leu His 210 215 220 Asn Glu Ala Phe Gly Leu Gly Asp Leu Pro Asn Leu Leu Gly Leu Val 225 230 235 240 Gly Asp Gln Leu Gly Asp Thr Glu Arg Lys Arg Arg His Ala Lys Pro 245 250 255 Gly Ser Tyr Ser Ile Glu Val Leu Leu Val Val Asp Asp Ser Val Val 260 265 270 Arg Phe His Gly Lys Glu His Val Gln Asn Tyr Val Leu Thr Leu Met 275 280 285 Asn Ile Val Asp Glu Ile Tyr His Asp Glu Ser Leu Gly Val His Ile 290 295 300 Asn Ile Ala Leu Val Arg Leu Ile Met Val Gly Tyr Arg Gln Ser Leu 305 310 315 320 Ser Leu Ile Glu Arg Gly Asn Pro Ser Arg Ser Leu Glu Gln Val Cys 325 330 335 Arg Trp Ala His Ser Gln Gln Arg Gln Asp Pro Ser His Ala Glu His 340 345 350 His Asp His Val Val Phe Leu Thr Arg Gln Asp Phe Gly Pro Ser Gly 355 360 365 Tyr Ala Pro Val Thr Gly Met Cys His Pro Leu Arg Ser Cys Ala Leu 370 375 380 Asn His Glu Asp Gly Phe Ser Ser Ala Phe Val Ile Ala His Glu Thr 385 390 395 400 Gly His Val Leu Gly Met Glu His Asp Gly Gln Gly Asn Gly Cys Ala 405 410 415 Asp Glu Thr Ser Leu Gly Ser Val Met Ala Pro Leu Val Gln Ala Ala 420 425 430 Phe His Arg Phe His Trp Ser Arg Cys Ser Lys Leu Glu Leu Ser Arg 435 440 445 Tyr Leu Pro Ser Tyr Asp Cys Leu Leu Asp Asp Pro Phe Asp Pro Ala 450 455 460 Trp Pro Gln Pro Pro Glu Leu Pro Gly Ile Asn Tyr Ser Met Asp Glu 465 470 475 480 Gln Cys Arg Phe Asp Phe Gly Ser Gly Tyr Gln Thr Cys Leu Ala Phe 485 490 495 Arg Thr Phe Glu Pro Cys Lys Gln Leu Trp Cys Ser His Pro Asp Asn 500 505 510 Pro Tyr Phe Cys Lys Thr Lys Lys Gly Pro Pro Leu Asp Gly Thr Glu 515 520 525 Cys Ala Pro Gly Lys Trp Cys Phe Lys Gly His Cys Ile Trp Lys Ser 530 535 540 Pro Glu Gln Thr Tyr Gly Gln Asp Gly Gly Trp Ser Ser Trp Thr Lys 545 550 555 560 Phe Gly Ser Cys Ser Arg Ser Cys Gly Gly Gly Val Arg Ser Arg Ser 565 570 575 Arg Ser Cys Asn Asn Pro Ser Pro Ala Tyr Gly Gly Arg Pro Cys Leu 580 585 590 Gly Pro Met Phe Glu Tyr Gln Val Cys Asn Ser Glu Glu Cys Pro Gly 595 600 605 Thr Tyr Glu Asp Phe Arg Ala Gln Gln Cys Ala Lys Arg Asn Ser Tyr 610 615 620 Tyr Val His Gln Asn Ala Lys His Ser Trp Val Pro Tyr Glu Pro Asp 625 630 635 640 Asp Asp Ala Gln Lys Cys Glu Leu Ile Cys Gln Ser Ala Asp Thr Gly 645 650 655 Asp Val Val Phe Met Asn Gln Val Val His Asp Gly Thr Arg Cys Ser 660 665 670 Tyr Arg Asp Pro Tyr Ser Val Cys Ala Arg Gly Glu Cys Val Pro Val 675 680 685 Gly Cys Asp Lys Glu Val Gly Ser Met Lys Ala Asp Asp Lys Cys Gly 690 695 700 Val Cys Gly Gly Asp Asn Ser His Cys Arg Thr Val Lys Gly Thr Leu 705 710 715 720 Gly Lys Ala Ser Lys Gln Ala Gly Ala Leu Lys Leu Val Gln Ile Pro 725 730 735 Ala Gly Ala Arg His Ile Gln Ile Glu Ala Leu Glu Lys Ser Pro His 740 745 750 Arg Ser Val Val Lys Asn Gln Val Thr Gly Ser Phe Ile Leu Asn Pro 755 760 765 Lys Gly Lys Glu Ala Thr Ser Arg Thr Phe Thr Ala Met Gly Leu Glu 770 775 780 Trp Glu Asp Ala Val Glu Asp Ala Lys Glu Ser Leu Lys Thr Ser Gly 785 790 795 800 Pro Leu Pro Glu Ala Ile Ala Ile Leu Ala Leu Pro Pro Thr Glu Gly 805 810 815 Gly Pro Arg Ser Ser Leu Ala Tyr Lys Tyr Val Ile His Glu Asp Leu 820 825 830 Leu Pro Leu Ile Gly Ser Asn Asn Val Leu Leu Glu Glu Met Asp Thr 835 840 845 Tyr Glu Trp Ala Leu Lys Ser Trp Ala Pro Cys Ser Lys Ala Cys Gly 850 855 860 Gly Gly Ile Gln Phe Thr Lys Tyr Gly Cys Arg Arg Arg Arg Asp His 865 870 875 880 His Met Val Gln Arg His Leu Cys Asp His Lys Lys Arg Pro Lys Pro 885 890 895 Ile Arg Arg Arg Cys Asn Gln His Pro Cys Ser Gln Pro Val Trp Val 900 905 910 Thr Glu Glu Trp Gly Ala Cys Ser Arg Ser Cys Gly Lys Leu Gly Val 915 920 925 Gln Thr Arg Gly Ile Gln Cys Leu Leu Pro Leu Ser Asn Gly Thr His 930 935 940 Lys Val Met Pro Ala Lys Ala Cys Ala Gly Asp Arg Pro Glu Ala Arg 945 950 955 960 Arg Pro Cys Leu Arg Val Pro Cys Pro Ala Gln Trp Arg Leu Gly Ala 965 970 975 Trp Ser Gln Cys Ser Ala Thr Cys Gly Glu Gly Ile Gln Gln Arg Gln 980 985 990 Val Val Cys Arg Thr Asn Ala Asn Ser Leu Gly His Cys Glu Gly Asp 995 1000 1005 Arg Pro Asp Thr Val Gln Val Cys Ser Leu Pro Ala Cys Gly Gly Asn 1010 1015 1020 His Gln Asn Ser Thr Val Arg Ala Asp Val Trp Glu Leu Gly Thr Pro 1025 1030 1035 1040 Glu Gly Gln Trp Val Pro Gln Ser Gly Pro Leu His Pro Ile Asn Lys 1045 1050 1055 Ile Ser Ser Thr Glu Pro Cys Thr Gly Asp Arg Ser Val Phe Cys Gln 1060 1065 1070 Met Glu Val Leu Asp Arg Tyr Cys Ser Ile Pro Gly Tyr His Arg Leu 1075 1080 1085 Cys Cys Val Ser Cys Ile Lys Lys Ala Ser Gly Pro Asn Pro Gly Pro 1090 1095 1100 Asp Pro Gly Pro Thr Ser Leu Pro Pro Phe Ser Thr Pro Gly Ser Pro 1105 1110 1115 1120 Leu Pro Gly Pro Gln Asp Pro Ala Asp Ala Ala Glu Pro Pro Gly Lys 1125 1130 1135 Pro Thr Gly Ser Glu Asp His Gln His Gly Arg Ala Thr Gln Leu Pro 1140 1145 1150 Gly Ala Leu Asp Thr Ser Ser Pro Gly Thr Gln His Pro Phe Ala Pro 1155 1160 1165 Glu Thr Pro Ile Pro Gly Ala Ser Trp Ser Ile Ser Pro Thr Thr Pro 1170 1175 1180 Gly Gly Leu Pro Trp Gly Trp Thr Gln Thr Pro Thr Pro Val Pro Glu 1185 1190 1195 1200 Asp Lys Gly Gln Pro Gly Glu Asp Leu Arg Pro Ala Arg Ala Ala Ala 1205 1210 1215 Arg Ala Leu 11 3651 DNA homo sapiens 11 atggctccac tccgcgcgct gctgtcctac ctgctgcctt tgcactgtgc gctctgcrcc 60 gccgcgggca gccggacccc agagctgcac ctctctggaa agctcagtga ctatggtgtg 120 acagtgccct gcagcacaga ctttcgggga cgcttcctct cccacgtggt gtctggccca 180 gcagcagcct ctgcagggag catggtagtg gacacgccac ccacactacc acgacactcc 240 agtcacctcc gggtggctcg cagccctctg cacccaggag ggaccctgtg gcctggcagg 300 gtggggcgcc actccctcta cttcaatgtc actgttttcg ggaaggaact gcacttgcgc 360 ctgcggccca atcggaggtt ggtagtgcca ggatcctcag tggagtggca ggaggatttt 420 cgggagctgt tccggcagcc cttacggcag gagtgtgtgt acactggagg tgtcactgga 480 atgcctgggg cagctgttgc catcagcaac tgtgacggat tggcgggcct catccgcaca 540 gacagcaccg acttcttcat tgagcctctg gagcggggcc agcaggagaa ggaggccagc 600 gggaggacac atgtggtgta ccgccgggag gccgtccagc aggagtgggc agaacctgac 660 ggggacctgc acaatgaagc ctttggcctg ggagaccttc ccaacctgct gggcctggtg 720 ggggaccagc tgggcgacac agagcggaag cggcggcatg ccaagccagg cagctacagc 780 atcgaggtgc tgctggtggt ggacgactcg gtggttcgct tccatggcaa ggagcatgtg 840 cagaactatg tcctcaccct catgaatatc gtagatgaga tttaccacga tgagtccctg 900 ggggttcata taaatattgc cctcgtccgc ttgatcatgg ttggctaccg acagtccctg 960 agcctgatcg agcgcgggaa cccctcacgc agcctggagc aggtgtgtcg ctgggcacac 1020 tcccagcagc gccaggaccc cagccacgct gagcaccatg accacgttgt gttcctcacc 1080 cggcaggact ttgggccctc agggtatgca cccgtcactg gcatgtgtca ccccctgagg 1140 agctgtgccc tcaaccatga ggatggcttc tcctcagcct tcgtgatagc tcatgagacc 1200 ggccacgtgc tcggcatgga gcatgacggt caggggaatg gctgtgcaga tgagaccagc 1260 ctgggcagcg tcatggcgcc cctggtgcag gctgccttcc accgcttcca ttggtcccgc 1320 tgcagcaagc tggagctcag ccgctacctc ccctcctacg actgcctcct cgatgacccc 1380 tttgatcctg cctggcccca gcccccagag ctgcctggga tcaactactc aatggatgag 1440 cagtgccgct ttgactttgg cagtggctac cagacctgct tggcattcag gacctttgag 1500 ccctgcaagc agctgtggtg cagccatcct gacaaccmgt ayttctgcaa gaccaagaag 1560 gggcccccgc tggatgggac tgagtgtgca cccggcaagt ggtgcttcaa aggtcactgc 1620 atctggaagt cgccggagca gacatatggc caggatggag gctggagctc ctggaccaag 1680 tttgggtcat gttcgcggtc atgtgggggc ggggtgcgat cccgcagccg gagctgcaac 1740 aacccctccc cagcctatgg aggccgccyg tgcttagggc ccatgttcga gtaccaggtc 1800 tgcaacagcg aggagtgccc tgggacctac gaggacttcc gggcccagca gtgtgccaag 1860 cgcaactcst actatgtgca ccagaatgcc aagcacagst gggtgcccta cgagcctgac 1920 gatgacgccc agaagtgtga gctgatctgc cagtcggcgg acacrgggga cgtggtgttc 1980 atgaaccagg tggttcacga tgggacacgc tgcagctacc gggacccata cagcgtctgt 2040 gcgcgtggcg agtgtgtgcc tgtcggctgt gacaaggagg tggggtccat gaaggcggat 2100 gacaagtgtg gagtctgcgg gggtgacaac tcccactgca ggactgtgaa ggggacgctg 2160 ggcaaggcct ccaagcaggc aggagctctc aagctggtgc agatcccagc aggtgccagg 2220 cacatccaga ttgaggcact ggagaagtcc ccccaccgsw ywgtggtgaa gaaccaggtc 2280 accggcagct tcatcctcaa ccccaagggc aaggaagcca caagccggac cttcaccgcc 2340 atgggcctgg agtgggagga tgcggtggag gatgccaagg aaagcctcaa gaccagcggg 2400 cccctgcctg aagccattgc catcctggct ctccccccaa ctgagggtgg cccccgcagc 2460 agcctggcct acaagtacgt catccatgag gacctgctgc cccttatcgg gagcaacaat 2520 gtgctcctgg aggagatgga cacctatgag tgggcgctca agagctgggc cccctgcagc 2580 aaggcctgtg gaggagggat ccagttcacc aaatacggct gccggcgcag acgagaccac 2640 cacatggtgc agcgacacct gtgtgaccac aagaagaggc ccaagcccat ccgccggcgc 2700 tgcaaccagc acccgtgctc tcagcctgtg tgggtgacgg aggagtgggg tgcctgcagc 2760 cggagctgtg ggaagctggg ggtgcagaca cgggggatac agtgcctgct gcccctctcc 2820 aatggaaccc acaaggtcat gccggccaaa gcctgcgccg gggaccggcc tgaggcccga 2880 cggccctgtc tccgagtgcc ctgcccagcc cagtggaggc tgggagcctg gtcccagtgc 2940 tctgccacct gtggagaggg catccagcag cggcaggtgg tgtgcaggac caacgccaac 3000 agcctcgggc attgcgaggg ggataggcca gacactgtcc aggtctgcar cctgcccgcc 3060 tgtggaggaa atcaccagaa ctccacggtg agggccgatg tctgggaact tgggacgcca 3120 gaggggcagt gggtgccaca atctgraccc ctacatccca ttaacaagat atcatcaatg 3180 tgtgcagcgg agccctgcac gggagacagg tctgtcttct gccagatgga agtgctcgat 3240 cgctactgct ccattcccgg ctaccaccgg ctctgctgtg tgtcctgcat caagaaggcc 3300 tcgggcccca accctggccc agaccctggc ccaacctcac tgcccccctt ctccactcct 3360 ggaagcccct taccaggacc ccaggaccct gcagatgctg cagagcctcc tggaaagcca 3420 acgggatcag aggaccatca gcatggccga gccacacagc tcccaggagc tctggataca 3480 agctccccag ggacccagca tccctttgcc cctgagacac caatccctgg agcatcctgg 3540 agcatctccc ctaccacccc cggggggctg ccttggggct ggactcagac acctacgcca 3600 gtccctgacc tgcccgggcg gccgctcgag ccctatagtg agtcgtatta g 3651 12 1216 PRT homo sapiens 12 Met Ala Pro Leu Arg Ala Leu Leu Ser Tyr Leu Leu Pro Leu His Cys 1 5 10 15 Ala Leu Cys Thr Ala Ala Gly Ser Arg Thr Pro Glu Leu His Leu Ser 20 25 30 Gly Lys Leu Ser Asp Tyr Gly Val Thr Val Pro Cys Ser Thr Asp Phe 35 40 45 Arg Gly Arg Phe Leu Ser His Val Val Ser Gly Pro Ala Ala Ala Ser 50 55 60 Ala Gly Ser Met Val Val Asp Thr Pro Pro Thr Leu Pro Arg His Ser 65 70 75 80 Ser His Leu Arg Val Ala Arg Ser Pro Leu His Pro Gly Gly Thr Leu 85 90 95 Trp Pro Gly Arg Val Gly Arg His Ser Leu Tyr Phe Asn Val Thr Val 100 105 110 Phe Gly Lys Glu Leu His Leu Arg Leu Arg Pro Asn Arg Arg Leu Val 115 120 125 Val Pro Gly Ser Ser Val Glu Trp Gln Glu Asp Phe Arg Glu Leu Phe 130 135 140 Arg Gln Pro Leu Arg Gln Glu Cys Val Tyr Thr Gly Gly Val Thr Gly 145 150 155 160 Met Pro Gly Ala Ala Val Ala Ile Ser Asn Cys Asp Gly Leu Ala Gly 165 170 175 Leu Ile Arg Thr Asp Ser Thr Asp Phe Phe Ile Glu Pro Leu Glu Arg 180 185 190 Gly Gln Gln Glu Lys Glu Ala Ser Gly Arg Thr His Val Val Tyr Arg 195 200 205 Arg Glu Ala Val Gln Gln Glu Trp Ala Glu Pro Asp Gly Asp Leu His 210 215 220 Asn Glu Ala Phe Gly Leu Gly Asp Leu Pro Asn Leu Leu Gly Leu Val 225 230 235 240 Gly Asp Gln Leu Gly Asp Thr Glu Arg Lys Arg Arg His Ala Lys Pro 245 250 255 Gly Ser Tyr Ser Ile Glu Val Leu Leu Val Val Asp Asp Ser Val Val 260 265 270 Arg Phe His Gly Lys Glu His Val Gln Asn Tyr Val Leu Thr Leu Met 275 280 285 Asn Ile Val Asp Glu Ile Tyr His Asp Glu Ser Leu Gly Val His Ile 290 295 300 Asn Ile Ala Leu Val Arg Leu Ile Met Val Gly Tyr Arg Gln Ser Leu 305 310 315 320 Ser Leu Ile Glu Arg Gly Asn Pro Ser Arg Ser Leu Glu Gln Val Cys 325 330 335 Arg Trp Ala His Ser Gln Gln Arg Gln Asp Pro Ser His Ala Glu His 340 345 350 His Asp His Val Val Phe Leu Thr Arg Gln Asp Phe Gly Pro Ser Gly 355 360 365 Tyr Ala Pro Val Thr Gly Met Cys His Pro Leu Arg Ser Cys Ala Leu 370 375 380 Asn His Glu Asp Gly Phe Ser Ser Ala Phe Val Ile Ala His Glu Thr 385 390 395 400 Gly His Val Leu Gly Met Glu His Asp Gly Gln Gly Asn Gly Cys Ala 405 410 415 Asp Glu Thr Ser Leu Gly Ser Val Met Ala Pro Leu Val Gln Ala Ala 420 425 430 Phe His Arg Phe His Trp Ser Arg Cys Ser Lys Leu Glu Leu Ser Arg 435 440 445 Tyr Leu Pro Ser Tyr Asp Cys Leu Leu Asp Asp Pro Phe Asp Pro Ala 450 455 460 Trp Pro Gln Pro Pro Glu Leu Pro Gly Ile Asn Tyr Ser Met Asp Glu 465 470 475 480 Gln Cys Arg Phe Asp Phe Gly Ser Gly Tyr Gln Thr Cys Leu Ala Phe 485 490 495 Arg Thr Phe Glu Pro Cys Lys Gln Leu Trp Cys Ser His Pro Asp Asn 500 505 510 Pro Tyr Phe Cys Lys Thr Lys Lys Gly Pro Pro Leu Asp Gly Thr Glu 515 520 525 Cys Ala Pro Gly Lys Trp Cys Phe Lys Gly His Cys Ile Trp Lys Ser 530 535 540 Pro Glu Gln Thr Tyr Gly Gln Asp Gly Gly Trp Ser Ser Trp Thr Lys 545 550 555 560 Phe Gly Ser Cys Ser Arg Ser Cys Gly Gly Gly Val Arg Ser Arg Ser 565 570 575 Arg Ser Cys Asn Asn Pro Ser Pro Ala Tyr Gly Gly Arg Pro Cys Leu 580 585 590 Gly Pro Met Phe Glu Tyr Gln Val Cys Asn Ser Glu Glu Cys Pro Gly 595 600 605 Thr Tyr Glu Asp Phe Arg Ala Gln Gln Cys Ala Lys Arg Asn Ser Tyr 610 615 620 Tyr Val His Gln Asn Ala Lys His Ser Trp Val Pro Tyr Glu Pro Asp 625 630 635 640 Asp Asp Ala Gln Lys Cys Glu Leu Ile Cys Gln Ser Ala Asp Thr Gly 645 650 655 Asp Val Val Phe Met Asn Gln Val Val His Asp Gly Thr Arg Cys Ser 660 665 670 Tyr Arg Asp Pro Tyr Ser Val Cys Ala Arg Gly Glu Cys Val Pro Val 675 680 685 Gly Cys Asp Lys Glu Val Gly Ser Met Lys Ala Asp Asp Lys Cys Gly 690 695 700 Val Cys Gly Gly Asp Asn Ser His Cys Arg Thr Val Lys Gly Thr Leu 705 710 715 720 Gly Lys Ala Ser Lys Gln Ala Gly Ala Leu Lys Leu Val Gln Ile Pro 725 730 735 Ala Gly Ala Arg His Ile Gln Ile Glu Ala Leu Glu Lys Ser Pro His 740 745 750 Arg Ser Val Val Lys Asn Gln Val Thr Gly Ser Phe Ile Leu Asn Pro 755 760 765 Lys Gly Lys Glu Ala Thr Ser Arg Thr Phe Thr Ala Met Gly Leu Glu 770 775 780 Trp Glu Asp Ala Val Glu Asp Ala Lys Glu Ser Leu Lys Thr Ser Gly 785 790 795 800 Pro Leu Pro Glu Ala Ile Ala Ile Leu Ala Leu Pro Pro Thr Glu Gly 805 810 815 Gly Pro Arg Ser Ser Leu Ala Tyr Lys Tyr Val Ile His Glu Asp Leu 820 825 830 Leu Pro Leu Ile Gly Ser Asn Asn Val Leu Leu Glu Glu Met Asp Thr 835 840 845 Tyr Glu Trp Ala Leu Lys Ser Trp Ala Pro Cys Ser Lys Ala Cys Gly 850 855 860 Gly Gly Ile Gln Phe Thr Lys Tyr Gly Cys Arg Arg Arg Arg Asp His 865 870 875 880 His Met Val Gln Arg His Leu Cys Asp His Lys Lys Arg Pro Lys Pro 885 890 895 Ile Arg Arg Arg Cys Asn Gln His Pro Cys Ser Gln Pro Val Trp Val 900 905 910 Thr Glu Glu Trp Gly Ala Cys Ser Arg Ser Cys Gly Lys Leu Gly Val 915 920 925 Gln Thr Arg Gly Ile Gln Cys Leu Leu Pro Leu Ser Asn Gly Thr His 930 935 940 Lys Val Met Pro Ala Lys Ala Cys Ala Gly Asp Arg Pro Glu Ala Arg 945 950 955 960 Arg Pro Cys Leu Arg Val Pro Cys Pro Ala Gln Trp Arg Leu Gly Ala 965 970 975 Trp Ser Gln Cys Ser Ala Thr Cys Gly Glu Gly Ile Gln Gln Arg Gln 980 985 990 Val Val Cys Arg Thr Asn Ala Asn Ser Leu Gly His Cys Glu Gly Asp 995 1000 1005 Arg Pro Asp Thr Val Gln Val Cys Ser Leu Pro Ala Cys Gly Gly Asn 1010 1015 1020 His Gln Asn Ser Thr Val Arg Ala Asp Val Trp Glu Leu Gly Thr Pro 1025 1030 1035 1040 Glu Gly Gln Trp Val Pro Gln Ser Gly Pro Leu His Pro Ile Asn Lys 1045 1050 1055 Ile Ser Ser Met Cys Ala Ala Glu Pro Cys Thr Gly Asp Arg Ser Val 1060 1065 1070 Phe Cys Gln Met Glu Val Leu Asp Arg Tyr Cys Ser Ile Pro Gly Tyr 1075 1080 1085 His Arg Leu Cys Cys Val Ser Cys Ile Lys Lys Ala Ser Gly Pro Asn 1090 1095 1100 Pro Gly Pro Asp Pro Gly Pro Thr Ser Leu Pro Pro Phe Ser Thr Pro 1105 1110 1115 1120 Gly Ser Pro Leu Pro Gly Pro Gln Asp Pro Ala Asp Ala Ala Glu Pro 1125 1130 1135 Pro Gly Lys Pro Thr Gly Ser Glu Asp His Gln His Gly Arg Ala Thr 1140 1145 1150 Gln Leu Pro Gly Ala Leu Asp Thr Ser Ser Pro Gly Thr Gln His Pro 1155 1160 1165 Phe Ala Pro Glu Thr Pro Ile Pro Gly Ala Ser Trp Ser Ile Ser Pro 1170 1175 1180 Thr Thr Pro Gly Gly Leu Pro Trp Gly Trp Thr Gln Thr Pro Thr Pro 1185 1190 1195 1200 Val Pro Asp Leu Pro Gly Arg Pro Leu Glu Pro Tyr Ser Glu Ser Tyr 1205 1210 1215 13 3642 DNA homo sapiens 13 atggctccac tccgcgcgct gctgtcctac ctgctgcctt tgcactgtgc gctctgcrcc 60 gccgcgggca gccggacccc agagctgcac ctctctggaa agctcagtga ctatggtgtg 120 acagtgccct gcagcacaga ctttcgggga cgcttcctct cccacgtggt gtctggccca 180 gcagcagcct ctgcagggag catggtagtg gacacgccac ccacactacc acgacactcc 240 agtcacctcc gggtggctcg cagccctctg cacccaggag ggaccctgtg gcctggcagg 300 gtggggcgcc actccctcta cttcaatgtc actgttttcg ggaaggaact gcacttgcgc 360 ctgcggccca atcggaggtt ggtagtgcca ggatcctcag tggagtggca ggaggatttt 420 cgggagctgt tccggcagcc cttacggcag gagtgtgtgt acactggagg tgtcactgga 480 atgcctgggg cagctgttgc catcagcaac tgtgacggat tggcgggcct catccgcaca 540 gacagcaccg acttcttcat tgagcctctg gagcggggcc agcaggagaa ggaggccagc 600 gggaggacac atgtggtgta ccgccgggag gccgtccagc aggagtgggc agaacctgac 660 ggggacctgc acaatgaagc ctttggcctg ggagaccttc ccaacctgct gggcctggtg 720 ggggaccagc tgggcgacac agagcggaag cggcggcatg ccaagccagg cagctacagc 780 atcgaggtgc tgctggtggt ggacgactcg gtggttcgct tccatggcaa ggagcatgtg 840 cagaactatg tcctcaccct catgaatatc gtagatgaga tttaccacga tgagtccctg 900 ggggttcata taaatattgc cctcgtccgc ttgatcatgg ttggctaccg acagtccctg 960 agcctgatcg agcgcgggaa cccctcacgc agcctggagc aggtgtgtcg ctgggcacac 1020 tcccagcagc gccaggaccc cagccacgct gagcaccatg accacgttgt gttcctcacc 1080 cggcaggact ttgggccctc agggtatgca cccgtcactg gcatgtgtca ccccctgagg 1140 agctgtgccc tcaaccatga ggatggcttc tcctcagcct tcgtgatagc tcatgagacc 1200 ggccacgtgc tcggcatgga gcatgacggt caggggaatg gctgtgcaga tgagaccagc 1260 ctgggcagcg tcatggcgcc cctggtgcag gctgccttcc accgcttcca ttggtcccgc 1320 tgcagcaagc tggagctcag ccgctacctc ccctcctacg actgcctcct cgatgacccc 1380 tttgatcctg cctggcccca gcccccagag ctgcctggga tcaactactc aatggatgag 1440 cagtgccgct ttgactttgg cagtggctac cagacctgct tggcattcag gacctttgag 1500 ccctgcaagc agctgtggtg cagccatcct gacaaccmgt ayttctgcaa gaccaagaag 1560 gggcccccgc tggatgggac tgagtgtgca cccggcaagt ggtgcttcaa aggtcactgc 1620 atctggaagt cgccggagca gacatatggc caggatggag gctggagctc ctggaccaag 1680 tttgggtcat gttcgcggtc atgtgggggc ggggtgcgat cccgcagccg gagctgcaac 1740 aacccctccc cagcctatgg aggccgccyg tgcttagggc ccatgttcga gtaccaggtc 1800 tgcaacagcg aggagtgccc tgggacctac gaggacttcc gggcccagca gtgtgccaag 1860 cgcaactcst actatgtgca ccagaatgcc aagcacagst gggtgcccta cgagcctgac 1920 gatgacgccc agaagtgtga gctgatctgc cagtcggcgg acacrgggga cgtggtgttc 1980 atgaaccagg tggttcacga tgggacacgc tgcagctacc gggacccata cagcgtctgt 2040 gcgcgtggcg agtgtgtgcc tgtcggctgt gacaaggagg tggggtccat gaaggcggat 2100 gacaagtgtg gagtctgcgg gggtgacaac tcccactgca ggactgtgaa ggggacgctg 2160 ggcaaggcct ccaagcaggc aggagctctc aagctggtgc agatcccagc aggtgccagg 2220 cacatccaga ttgaggcact ggagaagtcc ccccaccgsw ywgtggtgaa gaaccaggtc 2280 accggcagct tcatcctcaa ccccaagggc aaggaagcca caagccggac cttcaccgcc 2340 atgggcctgg agtgggagga tgcggtggag gatgccaagg aaagcctcaa gaccagcggg 2400 cccctgcctg aagccattgc catcctggct ctccccccaa ctgagggtgg cccccgcagc 2460 agcctggcct acaagtacgt catccatgag gacctgctgc cccttatcgg gagcaacaat 2520 gtgctcctgg aggagatgga cacctatgag tgggcgctca agagctgggc cccctgcagc 2580 aaggcctgtg gaggagggat ccagttcacc aaatacggct gccggcgcag acgagaccac 2640 cacatggtgc agcgacacct gtgtgaccac aagaagaggc ccaagcccat ccgccggcgc 2700 tgcaaccagc acccgtgctc tcagcctgtg tgggtgacgg aggagtgggg tgcctgcagc 2760 cggagctgtg ggaagctggg ggtgcagaca cgggggatac agtgcctgct gcccctctcc 2820 aatggaaccc acaaggtcat gccggccaaa gcctgcgccg gggaccggcc tgaggcccga 2880 cggccctgtc tccgagtgcc ctgcccagcc cagtggaggc tgggagcctg gtcccagtgc 2940 tctgccacct gtggagaggg catccagcag cggcaggtgg tgtgcaggac caacgccaac 3000 agcctcgggc attgcgaggg ggataggcca gacactgtcc aggtctgcar cctgcccgcc 3060 tgtggaggaa atcaccagaa ctccacggtg agggccgatg tctgggaact tgggacgcca 3120 gaggggcagt gggtgccaca atctgraccc ctacatccca ttaacaagat atcatcaacg 3180 gagccctgca cgggagacag gtctgtcttc tgccagatgg aagtgctcga tcgctactgc 3240 tccattcccg gctaccaccg gctctgctgt gtgtcctgca tcaagaaggc ctcgggcccc 3300 aaccctggcc cagaccctgg cccaacctca ctgcccccct tctccactcc tggaagcccc 3360 ttaccaggac cccaggaccc tgcagatgct gcagagcctc ctggaaagcc aacgggatca 3420 gaggaccatc agcatggccg agccacacag ctcccaggag ctctggatac aagctcccca 3480 gggacccagc atccctttgc ccctgagaca ccaatccctg gagcatcctg gagcatctcc 3540 cctaccaccc ccggggggct gccttggggc tggactcaga cacctacgcc agtccctgac 3600 ctgcccgggc ggccgctcga gccctatagt gagtcgtatt ag 3642 14 1213 PRT homo sapiens 14 Met Ala Pro Leu Arg Ala Leu Leu Ser Tyr Leu Leu Pro Leu His Cys 1 5 10 15 Ala Leu Cys Thr Ala Ala Gly Ser Arg Thr Pro Glu Leu His Leu Ser 20 25 30 Gly Lys Leu Ser Asp Tyr Gly Val Thr Val Pro Cys Ser Thr Asp Phe 35 40 45 Arg Gly Arg Phe Leu Ser His Val Val Ser Gly Pro Ala Ala Ala Ser 50 55 60 Ala Gly Ser Met Val Val Asp Thr Pro Pro Thr Leu Pro Arg His Ser 65 70 75 80 Ser His Leu Arg Val Ala Arg Ser Pro Leu His Pro Gly Gly Thr Leu 85 90 95 Trp Pro Gly Arg Val Gly Arg His Ser Leu Tyr Phe Asn Val Thr Val 100 105 110 Phe Gly Lys Glu Leu His Leu Arg Leu Arg Pro Asn Arg Arg Leu Val 115 120 125 Val Pro Gly Ser Ser Val Glu Trp Gln Glu Asp Phe Arg Glu Leu Phe 130 135 140 Arg Gln Pro Leu Arg Gln Glu Cys Val Tyr Thr Gly Gly Val Thr Gly 145 150 155 160 Met Pro Gly Ala Ala Val Ala Ile Ser Asn Cys Asp Gly Leu Ala Gly 165 170 175 Leu Ile Arg Thr Asp Ser Thr Asp Phe Phe Ile Glu Pro Leu Glu Arg 180 185 190 Gly Gln Gln Glu Lys Glu Ala Ser Gly Arg Thr His Val Val Tyr Arg 195 200 205 Arg Glu Ala Val Gln Gln Glu Trp Ala Glu Pro Asp Gly Asp Leu His 210 215 220 Asn Glu Ala Phe Gly Leu Gly Asp Leu Pro Asn Leu Leu Gly Leu Val 225 230 235 240 Gly Asp Gln Leu Gly Asp Thr Glu Arg Lys Arg Arg His Ala Lys Pro 245 250 255 Gly Ser Tyr Ser Ile Glu Val Leu Leu Val Val Asp Asp Ser Val Val 260 265 270 Arg Phe His Gly Lys Glu His Val Gln Asn Tyr Val Leu Thr Leu Met 275 280 285 Asn Ile Val Asp Glu Ile Tyr His Asp Glu Ser Leu Gly Val His Ile 290 295 300 Asn Ile Ala Leu Val Arg Leu Ile Met Val Gly Tyr Arg Gln Ser Leu 305 310 315 320 Ser Leu Ile Glu Arg Gly Asn Pro Ser Arg Ser Leu Glu Gln Val Cys 325 330 335 Arg Trp Ala His Ser Gln Gln Arg Gln Asp Pro Ser His Ala Glu His 340 345 350 His Asp His Val Val Phe Leu Thr Arg Gln Asp Phe Gly Pro Ser Gly 355 360 365 Tyr Ala Pro Val Thr Gly Met Cys His Pro Leu Arg Ser Cys Ala Leu 370 375 380 Asn His Glu Asp Gly Phe Ser Ser Ala Phe Val Ile Ala His Glu Thr 385 390 395 400 Gly His Val Leu Gly Met Glu His Asp Gly Gln Gly Asn Gly Cys Ala 405 410 415 Asp Glu Thr Ser Leu Gly Ser Val Met Ala Pro Leu Val Gln Ala Ala 420 425 430 Phe His Arg Phe His Trp Ser Arg Cys Ser Lys Leu Glu Leu Ser Arg 435 440 445 Tyr Leu Pro Ser Tyr Asp Cys Leu Leu Asp Asp Pro Phe Asp Pro Ala 450 455 460 Trp Pro Gln Pro Pro Glu Leu Pro Gly Ile Asn Tyr Ser Met Asp Glu 465 470 475 480 Gln Cys Arg Phe Asp Phe Gly Ser Gly Tyr Gln Thr Cys Leu Ala Phe 485 490 495 Arg Thr Phe Glu Pro Cys Lys Gln Leu Trp Cys Ser His Pro Asp Asn 500 505 510 Pro Tyr Phe Cys Lys Thr Lys Lys Gly Pro Pro Leu Asp Gly Thr Glu 515 520 525 Cys Ala Pro Gly Lys Trp Cys Phe Lys Gly His Cys Ile Trp Lys Ser 530 535 540 Pro Glu Gln Thr Tyr Gly Gln Asp Gly Gly Trp Ser Ser Trp Thr Lys 545 550 555 560 Phe Gly Ser Cys Ser Arg Ser Cys Gly Gly Gly Val Arg Ser Arg Ser 565 570 575 Arg Ser Cys Asn Asn Pro Ser Pro Ala Tyr Gly Gly Arg Pro Cys Leu 580 585 590 Gly Pro Met Phe Glu Tyr Gln Val Cys Asn Ser Glu Glu Cys Pro Gly 595 600 605 Thr Tyr Glu Asp Phe Arg Ala Gln Gln Cys Ala Lys Arg Asn Ser Tyr 610 615 620 Tyr Val His Gln Asn Ala Lys His Ser Trp Val Pro Tyr Glu Pro Asp 625 630 635 640 Asp Asp Ala Gln Lys Cys Glu Leu Ile Cys Gln Ser Ala Asp Thr Gly 645 650 655 Asp Val Val Phe Met Asn Gln Val Val His Asp Gly Thr Arg Cys Ser 660 665 670 Tyr Arg Asp Pro Tyr Ser Val Cys Ala Arg Gly Glu Cys Val Pro Val 675 680 685 Gly Cys Asp Lys Glu Val Gly Ser Met Lys Ala Asp Asp Lys Cys Gly 690 695 700 Val Cys Gly Gly Asp Asn Ser His Cys Arg Thr Val Lys Gly Thr Leu 705 710 715 720 Gly Lys Ala Ser Lys Gln Ala Gly Ala Leu Lys Leu Val Gln Ile Pro 725 730 735 Ala Gly Ala Arg His Ile Gln Ile Glu Ala Leu Glu Lys Ser Pro His 740 745 750 Arg Ser Val Val Lys Asn Gln Val Thr Gly Ser Phe Ile Leu Asn Pro 755 760 765 Lys Gly Lys Glu Ala Thr Ser Arg Thr Phe Thr Ala Met Gly Leu Glu 770 775 780 Trp Glu Asp Ala Val Glu Asp Ala Lys Glu Ser Leu Lys Thr Ser Gly 785 790 795 800 Pro Leu Pro Glu Ala Ile Ala Ile Leu Ala Leu Pro Pro Thr Glu Gly 805 810 815 Gly Pro Arg Ser Ser Leu Ala Tyr Lys Tyr Val Ile His Glu Asp Leu 820 825 830 Leu Pro Leu Ile Gly Ser Asn Asn Val Leu Leu Glu Glu Met Asp Thr 835 840 845 Tyr Glu Trp Ala Leu Lys Ser Trp Ala Pro Cys Ser Lys Ala Cys Gly 850 855 860 Gly Gly Ile Gln Phe Thr Lys Tyr Gly Cys Arg Arg Arg Arg Asp His 865 870 875 880 His Met Val Gln Arg His Leu Cys Asp His Lys Lys Arg Pro Lys Pro 885 890 895 Ile Arg Arg Arg Cys Asn Gln His Pro Cys Ser Gln Pro Val Trp Val 900 905 910 Thr Glu Glu Trp Gly Ala Cys Ser Arg Ser Cys Gly Lys Leu Gly Val 915 920 925 Gln Thr Arg Gly Ile Gln Cys Leu Leu Pro Leu Ser Asn Gly Thr His 930 935 940 Lys Val Met Pro Ala Lys Ala Cys Ala Gly Asp Arg Pro Glu Ala Arg 945 950 955 960 Arg Pro Cys Leu Arg Val Pro Cys Pro Ala Gln Trp Arg Leu Gly Ala 965 970 975 Trp Ser Gln Cys Ser Ala Thr Cys Gly Glu Gly Ile Gln Gln Arg Gln 980 985 990 Val Val Cys Arg Thr Asn Ala Asn Ser Leu Gly His Cys Glu Gly Asp 995 1000 1005 Arg Pro Asp Thr Val Gln Val Cys Ser Leu Pro Ala Cys Gly Gly Asn 1010 1015 1020 His Gln Asn Ser Thr Val Arg Ala Asp Val Trp Glu Leu Gly Thr Pro 1025 1030 1035 1040 Glu Gly Gln Trp Val Pro Gln Ser Gly Pro Leu His Pro Ile Asn Lys 1045 1050 1055 Ile Ser Ser Thr Glu Pro Cys Thr Gly Asp Arg Ser Val Phe Cys Gln 1060 1065 1070 Met Glu Val Leu Asp Arg Tyr Cys Ser Ile Pro Gly Tyr His Arg Leu 1075 1080 1085 Cys Cys Val Ser Cys Ile Lys Lys Ala Ser Gly Pro Asn Pro Gly Pro 1090 1095 1100 Asp Pro Gly Pro Thr Ser Leu Pro Pro Phe Ser Thr Pro Gly Ser Pro 1105 1110 1115 1120 Leu Pro Gly Pro Gln Asp Pro Ala Asp Ala Ala Glu Pro Pro Gly Lys 1125 1130 1135 Pro Thr Gly Ser Glu Asp His Gln His Gly Arg Ala Thr Gln Leu Pro 1140 1145 1150 Gly Ala Leu Asp Thr Ser Ser Pro Gly Thr Gln His Pro Phe Ala Pro 1155 1160 1165 Glu Thr Pro Ile Pro Gly Ala Ser Trp Ser Ile Ser Pro Thr Thr Pro 1170 1175 1180 Gly Gly Leu Pro Trp Gly Trp Thr Gln Thr Pro Thr Pro Val Pro Asp 1185 1190 1195 1200 Leu Pro Gly Arg Pro Leu Glu Pro Tyr Ser Glu Ser Tyr 1205 1210 15 3708 DNA homo sapiens 15 atggctccac tccgcgcgct gctgtcctac ctgctgcctt tgcactgtgc gctctgcrcc 60 gccgcgggca gccggacccc agagctgcac ctctctggaa agctcagtga ctatggtgtg 120 acagtgccct gcagcacaga ctttcgggga cgcttcctct cccacgtggt gtctggccca 180 gcagcagcct ctgcagggag catggtagtg gacacgccac ccacactacc acgacactcc 240 agtcacctcc gggtggctcg cagccctctg cacccaggag ggaccctgtg gcctggcagg 300 gtggggcgcc actccctcta cttcaatgtc actgttttcg ggaaggaact gcacttgcgc 360 ctgcggccca atcggaggtt ggtagtgcca ggatcctcag tggagtggca ggaggatttt 420 cgggagctgt tccggcagcc cttacggcag gagtgtgtgt acactggagg tgtcactgga 480 atgcctgggg cagctgttgc catcagcaac tgtgacggat tggcgggcct catccgcaca 540 gacagcaccg acttcttcat tgagcctctg gagcggggcc agcaggagaa ggaggccagc 600 gggaggacac atgtggtgta ccgccgggag gccgtccagc aggagtgggc agaacctgac 660 ggggacctgc acaatgaagc ctttggcctg ggagaccttc ccaacctgct gggcctggtg 720 ggggaccagc tgggcgacac agagcggaag cggcggcatg ccaagccagg cagctacagc 780 atcgaggtgc tgctggtggt ggacgactcg gtggttcgct tccatggcaa ggagcatgtg 840 cagaactatg tcctcaccct catgaatatc gtagatgaga tttaccacga tgagtccctg 900 ggggttcata taaatattgc cctcgtccgc ttgatcatgg ttggctaccg acagtccctg 960 agcctgatcg agcgcgggaa cccctcacgc agcctggagc aggtgtgtcg ctgggcacac 1020 tcccagcagc gccaggaccc cagccacgct gagcaccatg accacgttgt gttcctcacc 1080 cggcaggact ttgggccctc agggtatgca cccgtcactg gcatgtgtca ccccctgagg 1140 agctgtgccc tcaaccatga ggatggcttc tcctcagcct tcgtgatagc tcatgagacc 1200 ggccacgtgc tcggcatgga gcatgacggt caggggaatg gctgtgcaga tgagaccagc 1260 ctgggcagcg tcatggcgcc cctggtgcag gctgccttcc accgcttcca ttggtcccgc 1320 tgcagcaagc tggagctcag ccgctacctc ccctcctacg actgcctcct cgatgacccc 1380 tttgatcctg cctggcccca gcccccagag ctgcctggga tcaactactc aatggatgag 1440 cagtgccgct ttgactttgg cagtggctac cagacctgct tggcattcag gacctttgag 1500 ccctgcaagc agctgtggtg cagccatcct gacaaccmgt ayttctgcaa gaccaagaag 1560 gggcccccgc tggatgggac tgagtgtgca cccggcaagt ggtgcttcaa aggtcactgc 1620 atctggaagt cgccggagca gacatatggc caggatggag gctggagctc ctggaccaag 1680 tttgggtcat gttcgcggtc atgtgggggc ggggtgcgat cccgcagccg gagctgcaac 1740 aacccctccc cagcctatgg aggccgccyg tgcttagggc ccatgttcga gtaccaggtc 1800 tgcaacagcg aggagtgccc tgggacctac gaggacttcc gggcccagca gtgtgccaag 1860 cgcaactcst actatgtgca ccagaatgcc aagcacagst gggtgcccta cgagcctgac 1920 gatgacgccc agaagtgtga gctgatctgc cagtcggcgg acacrgggga cgtggtgttc 1980 atgaaccagg tggttcacga tgggacacgc tgcagctacc gggacccata cagcgtctgt 2040 gcgcgtggcg agtgtgtgcc tgtcggctgt gacaaggagg tggggtccat gaaggcggat 2100 gacaagtgtg gagtctgcgg gggtgacaac tcccactgca ggactgtgaa ggggacgctg 2160 ggcaaggcct ccaagcaggc aggagctctc aagctggtgc agatcccagc aggtgccagg 2220 cacatccaga ttgaggcact ggagaagtcc ccccaccgsw ywgtggtgaa gaaccaggtc 2280 accggcagct tcatcctcaa ccccaagggc aaggaagcca caagccggac cttcaccgcc 2340 atgggcctgg agtgggagga tgcggtggag gatgccaagg aaagcctcaa gaccagcggg 2400 cccctgcctg aagccattgc catcctggct ctccccccaa ctgagggtgg cccccgcagc 2460 agcctggcct acaagtacgt catccatgag gacctgctgc cccttatcgg gagcaacaat 2520 gtgctcctgg aggagatgga cacctatgag tgggcgctca agagctgggc cccctgcagc 2580 aaggcctgtg gaggagggat ccagttcacc aaatacggct gccggcgcag acgagaccac 2640 cacatggtgc agcgacacct gtgtgaccac aagaagaggc ccaagcccat ccgccggcgc 2700 tgcaaccagc acccgtgctc tcagcctgtg tgggtgacgg aggagtgggg tgcctgcagc 2760 cggagctgtg ggaagctggg ggtgcagaca cgggggatac agtgcctgct gcccctctcc 2820 aatggaaccc acaaggtcat gccggccaaa gcctgcgccg gggaccggcc tgaggcccga 2880 cggccctgtc tccgagtgcc ctgcccagcc cagtggaggc tgggagcctg gtcccagtgc 2940 tctgccacct gtggagaggg catccagcag cggcaggtgg tgtgcaggac caacgccaac 3000 agcctcgggc attgcgaggg ggataggcca gacactgtcc aggtctgcar cctgcccgcc 3060 tgtggaggaa atcaccagaa ctccacggtg agggccgatg tctgggaact tgggacgcca 3120 gaggggcagt gggtgccaca atctgraccc ctacatccca ttaacaagat atcatcaatg 3180 tgtgcagcgg agccctgcac gggagacagg tctgtcttct gccagatgga agtgctcgat 3240 cgctactgct ccattcccgg ctaccaccgg ctctgctgtg tgtcctgcat caagaaggcc 3300 tcgggcccca accctggccc agaccctggc ccaacctcac tgcccccctt ctccactcct 3360 ggaagcccct taccaggacc ccaggaccct gcagatgctg cagagcctcc tggaaagcca 3420 acgggatcag aggaccatca gcatggccga gccacacagc tcccaggagc tctggataca 3480 agctccccag ggacccagca tccctttgcc cctgagacac caatccctgg agcatcctgg 3540 agcatctccc ctaccacccc cggggggctg ccttggggct ggactcagac acctacgcca 3600 gtccctgagg acaaagggca acctggagaa gacctgagac atcccggcac cagcctccct 3660 gctgacctgc ccgggcggcc gcccgagccc tatagtgagt ctgattag 3708 16 1235 PRT homo sapiens 16 Met Ala Pro Leu Arg Ala Leu Leu Ser Tyr Leu Leu Pro Leu His Cys 1 5 10 15 Ala Leu Cys Thr Ala Ala Gly Ser Arg Thr Pro Glu Leu His Leu Ser 20 25 30 Gly Lys Leu Ser Asp Tyr Gly Val Thr Val Pro Cys Ser Thr Asp Phe 35 40 45 Arg Gly Arg Phe Leu Ser His Val Val Ser Gly Pro Ala Ala Ala Ser 50 55 60 Ala Gly Ser Met Val Val Asp Thr Pro Pro Thr Leu Pro Arg His Ser 65 70 75 80 Ser His Leu Arg Val Ala Arg Ser Pro Leu His Pro Gly Gly Thr Leu 85 90 95 Trp Pro Gly Arg Val Gly Arg His Ser Leu Tyr Phe Asn Val Thr Val 100 105 110 Phe Gly Lys Glu Leu His Leu Arg Leu Arg Pro Asn Arg Arg Leu Val 115 120 125 Val Pro Gly Ser Ser Val Glu Trp Gln Glu Asp Phe Arg Glu Leu Phe 130 135 140 Arg Gln Pro Leu Arg Gln Glu Cys Val Tyr Thr Gly Gly Val Thr Gly 145 150 155 160 Met Pro Gly Ala Ala Val Ala Ile Ser Asn Cys Asp Gly Leu Ala Gly 165 170 175 Leu Ile Arg Thr Asp Ser Thr Asp Phe Phe Ile Glu Pro Leu Glu Arg 180 185 190 Gly Gln Gln Glu Lys Glu Ala Ser Gly Arg Thr His Val Val Tyr Arg 195 200 205 Arg Glu Ala Val Gln Gln Glu Trp Ala Glu Pro Asp Gly Asp Leu His 210 215 220 Asn Glu Ala Phe Gly Leu Gly Asp Leu Pro Asn Leu Leu Gly Leu Val 225 230 235 240 Gly Asp Gln Leu Gly Asp Thr Glu Arg Lys Arg Arg His Ala Lys Pro 245 250 255 Gly Ser Tyr Ser Ile Glu Val Leu Leu Val Val Asp Asp Ser Val Val 260 265 270 Arg Phe His Gly Lys Glu His Val Gln Asn Tyr Val Leu Thr Leu Met 275 280 285 Asn Ile Val Asp Glu Ile Tyr His Asp Glu Ser Leu Gly Val His Ile 290 295 300 Asn Ile Ala Leu Val Arg Leu Ile Met Val Gly Tyr Arg Gln Ser Leu 305 310 315 320 Ser Leu Ile Glu Arg Gly Asn Pro Ser Arg Ser Leu Glu Gln Val Cys 325 330 335 Arg Trp Ala His Ser Gln Gln Arg Gln Asp Pro Ser His Ala Glu His 340 345 350 His Asp His Val Val Phe Leu Thr Arg Gln Asp Phe Gly Pro Ser Gly 355 360 365 Tyr Ala Pro Val Thr Gly Met Cys His Pro Leu Arg Ser Cys Ala Leu 370 375 380 Asn His Glu Asp Gly Phe Ser Ser Ala Phe Val Ile Ala His Glu Thr 385 390 395 400 Gly His Val Leu Gly Met Glu His Asp Gly Gln Gly Asn Gly Cys Ala 405 410 415 Asp Glu Thr Ser Leu Gly Ser Val Met Ala Pro Leu Val Gln Ala Ala 420 425 430 Phe His Arg Phe His Trp Ser Arg Cys Ser Lys Leu Glu Leu Ser Arg 435 440 445 Tyr Leu Pro Ser Tyr Asp Cys Leu Leu Asp Asp Pro Phe Asp Pro Ala 450 455 460 Trp Pro Gln Pro Pro Glu Leu Pro Gly Ile Asn Tyr Ser Met Asp Glu 465 470 475 480 Gln Cys Arg Phe Asp Phe Gly Ser Gly Tyr Gln Thr Cys Leu Ala Phe 485 490 495 Arg Thr Phe Glu Pro Cys Lys Gln Leu Trp Cys Ser His Pro Asp Asn 500 505 510 Pro Tyr Phe Cys Lys Thr Lys Lys Gly Pro Pro Leu Asp Gly Thr Glu 515 520 525 Cys Ala Pro Gly Lys Trp Cys Phe Lys Gly His Cys Ile Trp Lys Ser 530 535 540 Pro Glu Gln Thr Tyr Gly Gln Asp Gly Gly Trp Ser Ser Trp Thr Lys 545 550 555 560 Phe Gly Ser Cys Ser Arg Ser Cys Gly Gly Gly Val Arg Ser Arg Ser 565 570 575 Arg Ser Cys Asn Asn Pro Ser Pro Ala Tyr Gly Gly Arg Pro Cys Leu 580 585 590 Gly Pro Met Phe Glu Tyr Gln Val Cys Asn Ser Glu Glu Cys Pro Gly 595 600 605 Thr Tyr Glu Asp Phe Arg Ala Gln Gln Cys Ala Lys Arg Asn Ser Tyr 610 615 620 Tyr Val His Gln Asn Ala Lys His Ser Trp Val Pro Tyr Glu Pro Asp 625 630 635 640 Asp Asp Ala Gln Lys Cys Glu Leu Ile Cys Gln Ser Ala Asp Thr Gly 645 650 655 Asp Val Val Phe Met Asn Gln Val Val His Asp Gly Thr Arg Cys Ser 660 665 670 Tyr Arg Asp Pro Tyr Ser Val Cys Ala Arg Gly Glu Cys Val Pro Val 675 680 685 Gly Cys Asp Lys Glu Val Gly Ser Met Lys Ala Asp Asp Lys Cys Gly 690 695 700 Val Cys Gly Gly Asp Asn Ser His Cys Arg Thr Val Lys Gly Thr Leu 705 710 715 720 Gly Lys Ala Ser Lys Gln Ala Gly Ala Leu Lys Leu Val Gln Ile Pro 725 730 735 Ala Gly Ala Arg His Ile Gln Ile Glu Ala Leu Glu Lys Ser Pro His 740 745 750 Arg Ser Val Val Lys Asn Gln Val Thr Gly Ser Phe Ile Leu Asn Pro 755 760 765 Lys Gly Lys Glu Ala Thr Ser Arg Thr Phe Thr Ala Met Gly Leu Glu 770 775 780 Trp Glu Asp Ala Val Glu Asp Ala Lys Glu Ser Leu Lys Thr Ser Gly 785 790 795 800 Pro Leu Pro Glu Ala Ile Ala Ile Leu Ala Leu Pro Pro Thr Glu Gly 805 810 815 Gly Pro Arg Ser Ser Leu Ala Tyr Lys Tyr Val Ile His Glu Asp Leu 820 825 830 Leu Pro Leu Ile Gly Ser Asn Asn Val Leu Leu Glu Glu Met Asp Thr 835 840 845 Tyr Glu Trp Ala Leu Lys Ser Trp Ala Pro Cys Ser Lys Ala Cys Gly 850 855 860 Gly Gly Ile Gln Phe Thr Lys Tyr Gly Cys Arg Arg Arg Arg Asp His 865 870 875 880 His Met Val Gln Arg His Leu Cys Asp His Lys Lys Arg Pro Lys Pro 885 890 895 Ile Arg Arg Arg Cys Asn Gln His Pro Cys Ser Gln Pro Val Trp Val 900 905 910 Thr Glu Glu Trp Gly Ala Cys Ser Arg Ser Cys Gly Lys Leu Gly Val 915 920 925 Gln Thr Arg Gly Ile Gln Cys Leu Leu Pro Leu Ser Asn Gly Thr His 930 935 940 Lys Val Met Pro Ala Lys Ala Cys Ala Gly Asp Arg Pro Glu Ala Arg 945 950 955 960 Arg Pro Cys Leu Arg Val Pro Cys Pro Ala Gln Trp Arg Leu Gly Ala 965 970 975 Trp Ser Gln Cys Ser Ala Thr Cys Gly Glu Gly Ile Gln Gln Arg Gln 980 985 990 Val Val Cys Arg Thr Asn Ala Asn Ser Leu Gly His Cys Glu Gly Asp 995 1000 1005 Arg Pro Asp Thr Val Gln Val Cys Ser Leu Pro Ala Cys Gly Gly Asn 1010 1015 1020 His Gln Asn Ser Thr Val Arg Ala Asp Val Trp Glu Leu Gly Thr Pro 1025 1030 1035 1040 Glu Gly Gln Trp Val Pro Gln Ser Gly Pro Leu His Pro Ile Asn Lys 1045 1050 1055 Ile Ser Ser Met Cys Ala Ala Glu Pro Cys Thr Gly Asp Arg Ser Val 1060 1065 1070 Phe Cys Gln Met Glu Val Leu Asp Arg Tyr Cys Ser Ile Pro Gly Tyr 1075 1080 1085 His Arg Leu Cys Cys Val Ser Cys Ile Lys Lys Ala Ser Gly Pro Asn 1090 1095 1100 Pro Gly Pro Asp Pro Gly Pro Thr Ser Leu Pro Pro Phe Ser Thr Pro 1105 1110 1115 1120 Gly Ser Pro Leu Pro Gly Pro Gln Asp Pro Ala Asp Ala Ala Glu Pro 1125 1130 1135 Pro Gly Lys Pro Thr Gly Ser Glu Asp His Gln His Gly Arg Ala Thr 1140 1145 1150 Gln Leu Pro Gly Ala Leu Asp Thr Ser Ser Pro Gly Thr Gln His Pro 1155 1160 1165 Phe Ala Pro Glu Thr Pro Ile Pro Gly Ala Ser Trp Ser Ile Ser Pro 1170 1175 1180 Thr Thr Pro Gly Gly Leu Pro Trp Gly Trp Thr Gln Thr Pro Thr Pro 1185 1190 1195 1200 Val Pro Glu Asp Lys Gly Gln Pro Gly Glu Asp Leu Arg His Pro Gly 1205 1210 1215 Thr Ser Leu Pro Ala Asp Leu Pro Gly Arg Pro Pro Glu Pro Tyr Ser 1220 1225 1230 Glu Ser Asp 1235 17 3699 DNA homo sapiens 17 atggctccac tccgcgcgct gctgtcctac ctgctgcctt tgcactgtgc gctctgcrcc 60 gccgcgggca gccggacccc agagctgcac ctctctggaa agctcagtga ctatggtgtg 120 acagtgccct gcagcacaga ctttcgggga cgcttcctct cccacgtggt gtctggccca 180 gcagcagcct ctgcagggag catggtagtg gacacgccac ccacactacc acgacactcc 240 agtcacctcc gggtggctcg cagccctctg cacccaggag ggaccctgtg gcctggcagg 300 gtggggcgcc actccctcta cttcaatgtc actgttttcg ggaaggaact gcacttgcgc 360 ctgcggccca atcggaggtt ggtagtgcca ggatcctcag tggagtggca ggaggatttt 420 cgggagctgt tccggcagcc cttacggcag gagtgtgtgt acactggagg tgtcactgga 480 atgcctgggg cagctgttgc catcagcaac tgtgacggat tggcgggcct catccgcaca 540 gacagcaccg acttcttcat tgagcctctg gagcggggcc agcaggagaa ggaggccagc 600 gggaggacac atgtggtgta ccgccgggag gccgtccagc aggagtgggc agaacctgac 660 ggggacctgc acaatgaagc ctttggcctg ggagaccttc ccaacctgct gggcctggtg 720 ggggaccagc tgggcgacac agagcggaag cggcggcatg ccaagccagg cagctacagc 780 atcgaggtgc tgctggtggt ggacgactcg gtggttcgct tccatggcaa ggagcatgtg 840 cagaactatg tcctcaccct catgaatatc gtagatgaga tttaccacga tgagtccctg 900 ggggttcata taaatattgc cctcgtccgc ttgatcatgg ttggctaccg acagtccctg 960 agcctgatcg agcgcgggaa cccctcacgc agcctggagc aggtgtgtcg ctgggcacac 1020 tcccagcagc gccaggaccc cagccacgct gagcaccatg accacgttgt gttcctcacc 1080 cggcaggact ttgggccctc agggtatgca cccgtcactg gcatgtgtca ccccctgagg 1140 agctgtgccc tcaaccatga ggatggcttc tcctcagcct tcgtgatagc tcatgagacc 1200 ggccacgtgc tcggcatgga gcatgacggt caggggaatg gctgtgcaga tgagaccagc 1260 ctgggcagcg tcatggcgcc cctggtgcag gctgccttcc accgcttcca ttggtcccgc 1320 tgcagcaagc tggagctcag ccgctacctc ccctcctacg actgcctcct cgatgacccc 1380 tttgatcctg cctggcccca gcccccagag ctgcctggga tcaactactc aatggatgag 1440 cagtgccgct ttgactttgg cagtggctac cagacctgct tggcattcag gacctttgag 1500 ccctgcaagc agctgtggtg cagccatcct gacaaccmgt ayttctgcaa gaccaagaag 1560 gggcccccgc tggatgggac tgagtgtgca cccggcaagt ggtgcttcaa aggtcactgc 1620 atctggaagt cgccggagca gacatatggc caggatggag gctggagctc ctggaccaag 1680 tttgggtcat gttcgcggtc atgtgggggc ggggtgcgat cccgcagccg gagctgcaac 1740 aacccctccc cagcctatgg aggccgccyg tgcttagggc ccatgttcga gtaccaggtc 1800 tgcaacagcg aggagtgccc tgggacctac gaggacttcc gggcccagca gtgtgccaag 1860 cgcaactcst actatgtgca ccagaatgcc aagcacagst gggtgcccta cgagcctgac 1920 gatgacgccc agaagtgtga gctgatctgc cagtcggcgg acacrgggga cgtggtgttc 1980 atgaaccagg tggttcacga tgggacacgc tgcagctacc gggacccata cagcgtctgt 2040 gcgcgtggcg agtgtgtgcc tgtcggctgt gacaaggagg tggggtccat gaaggcggat 2100 gacaagtgtg gagtctgcgg gggtgacaac tcccactgca ggactgtgaa ggggacgctg 2160 ggcaaggcct ccaagcaggc aggagctctc aagctggtgc agatcccagc aggtgccagg 2220 cacatccaga ttgaggcact ggagaagtcc ccccaccgsw ywgtggtgaa gaaccaggtc 2280 accggcagct tcatcctcaa ccccaagggc aaggaagcca caagccggac cttcaccgcc 2340 atgggcctgg agtgggagga tgcggtggag gatgccaagg aaagcctcaa gaccagcggg 2400 cccctgcctg aagccattgc catcctggct ctccccccaa ctgagggtgg cccccgcagc 2460 agcctggcct acaagtacgt catccatgag gacctgctgc cccttatcgg gagcaacaat 2520 gtgctcctgg aggagatgga cacctatgag tgggcgctca agagctgggc cccctgcagc 2580 aaggcctgtg gaggagggat ccagttcacc aaatacggct gccggcgcag acgagaccac 2640 cacatggtgc agcgacacct gtgtgaccac aagaagaggc ccaagcccat ccgccggcgc 2700 tgcaaccagc acccgtgctc tcagcctgtg tgggtgacgg aggagtgggg tgcctgcagc 2760 cggagctgtg ggaagctggg ggtgcagaca cgggggatac agtgcctgct gcccctctcc 2820 aatggaaccc acaaggtcat gccggccaaa gcctgcgccg gggaccggcc tgaggcccga 2880 cggccctgtc tccgagtgcc ctgcccagcc cagtggaggc tgggagcctg gtcccagtgc 2940 tctgccacct gtggagaggg catccagcag cggcaggtgg tgtgcaggac caacgccaac 3000 agcctcgggc attgcgaggg ggataggcca gacactgtcc aggtctgcar cctgcccgcc 3060 tgtggaggaa atcaccagaa ctccacggtg agggccgatg tctgggaact tgggacgcca 3120 gaggggcagt gggtgccaca atctgraccc ctacatccca ttaacaagat atcatcaacg 3180 gagccctgca cgggagacag gtctgtcttc tgccagatgg aagtgctcga tcgctactgc 3240 tccattcccg gctaccaccg gctctgctgt gtgtcctgca tcaagaaggc ctcgggcccc 3300 aaccctggcc cagaccctgg cccaacctca ctgcccccct tctccactcc tggaagcccc 3360 ttaccaggac cccaggaccc tgcagatgct gcagagcctc ctggaaagcc aacgggatca 3420 gaggaccatc agcatggccg agccacacag ctcccaggag ctctggatac aagctcccca 3480 gggacccagc atccctttgc ccctgagaca ccaatccctg gagcatcctg gagcatctcc 3540 cctaccaccc ccggggggct gccttggggc tggactcaga cacctacgcc agtccctgag 3600 gacaaagggc aacctggaga agacctgaga catcccggca ccagcctccc tgctgacctg 3660 cccgggcggc cgcccgagcc ctatagtgag tctgattag 3699 18 1232 PRT homo sapiens 18 Met Ala Pro Leu Arg Ala Leu Leu Ser Tyr Leu Leu Pro Leu His Cys 1 5 10 15 Ala Leu Cys Thr Ala Ala Gly Ser Arg Thr Pro Glu Leu His Leu Ser 20 25 30 Gly Lys Leu Ser Asp Tyr Gly Val Thr Val Pro Cys Ser Thr Asp Phe 35 40 45 Arg Gly Arg Phe Leu Ser His Val Val Ser Gly Pro Ala Ala Ala Ser 50 55 60 Ala Gly Ser Met Val Val Asp Thr Pro Pro Thr Leu Pro Arg His Ser 65 70 75 80 Ser His Leu Arg Val Ala Arg Ser Pro Leu His Pro Gly Gly Thr Leu 85 90 95 Trp Pro Gly Arg Val Gly Arg His Ser Leu Tyr Phe Asn Val Thr Val 100 105 110 Phe Gly Lys Glu Leu His Leu Arg Leu Arg Pro Asn Arg Arg Leu Val 115 120 125 Val Pro Gly Ser Ser Val Glu Trp Gln Glu Asp Phe Arg Glu Leu Phe 130 135 140 Arg Gln Pro Leu Arg Gln Glu Cys Val Tyr Thr Gly Gly Val Thr Gly 145 150 155 160 Met Pro Gly Ala Ala Val Ala Ile Ser Asn Cys Asp Gly Leu Ala Gly 165 170 175 Leu Ile Arg Thr Asp Ser Thr Asp Phe Phe Ile Glu Pro Leu Glu Arg 180 185 190 Gly Gln Gln Glu Lys Glu Ala Ser Gly Arg Thr His Val Val Tyr Arg 195 200 205 Arg Glu Ala Val Gln Gln Glu Trp Ala Glu Pro Asp Gly Asp Leu His 210 215 220 Asn Glu Ala Phe Gly Leu Gly Asp Leu Pro Asn Leu Leu Gly Leu Val 225 230 235 240 Gly Asp Gln Leu Gly Asp Thr Glu Arg Lys Arg Arg His Ala Lys Pro 245 250 255 Gly Ser Tyr Ser Ile Glu Val Leu Leu Val Val Asp Asp Ser Val Val 260 265 270 Arg Phe His Gly Lys Glu His Val Gln Asn Tyr Val Leu Thr Leu Met 275 280 285 Asn Ile Val Asp Glu Ile Tyr His Asp Glu Ser Leu Gly Val His Ile 290 295 300 Asn Ile Ala Leu Val Arg Leu Ile Met Val Gly Tyr Arg Gln Ser Leu 305 310 315 320 Ser Leu Ile Glu Arg Gly Asn Pro Ser Arg Ser Leu Glu Gln Val Cys 325 330 335 Arg Trp Ala His Ser Gln Gln Arg Gln Asp Pro Ser His Ala Glu His 340 345 350 His Asp His Val Val Phe Leu Thr Arg Gln Asp Phe Gly Pro Ser Gly 355 360 365 Tyr Ala Pro Val Thr Gly Met Cys His Pro Leu Arg Ser Cys Ala Leu 370 375 380 Asn His Glu Asp Gly Phe Ser Ser Ala Phe Val Ile Ala His Glu Thr 385 390 395 400 Gly His Val Leu Gly Met Glu His Asp Gly Gln Gly Asn Gly Cys Ala 405 410 415 Asp Glu Thr Ser Leu Gly Ser Val Met Ala Pro Leu Val Gln Ala Ala 420 425 430 Phe His Arg Phe His Trp Ser Arg Cys Ser Lys Leu Glu Leu Ser Arg 435 440 445 Tyr Leu Pro Ser Tyr Asp Cys Leu Leu Asp Asp Pro Phe Asp Pro Ala 450 455 460 Trp Pro Gln Pro Pro Glu Leu Pro Gly Ile Asn Tyr Ser Met Asp Glu 465 470 475 480 Gln Cys Arg Phe Asp Phe Gly Ser Gly Tyr Gln Thr Cys Leu Ala Phe 485 490 495 Arg Thr Phe Glu Pro Cys Lys Gln Leu Trp Cys Ser His Pro Asp Asn 500 505 510 Pro Tyr Phe Cys Lys Thr Lys Lys Gly Pro Pro Leu Asp Gly Thr Glu 515 520 525 Cys Ala Pro Gly Lys Trp Cys Phe Lys Gly His Cys Ile Trp Lys Ser 530 535 540 Pro Glu Gln Thr Tyr Gly Gln Asp Gly Gly Trp Ser Ser Trp Thr Lys 545 550 555 560 Phe Gly Ser Cys Ser Arg Ser Cys Gly Gly Gly Val Arg Ser Arg Ser 565 570 575 Arg Ser Cys Asn Asn Pro Ser Pro Ala Tyr Gly Gly Arg Pro Cys Leu 580 585 590 Gly Pro Met Phe Glu Tyr Gln Val Cys Asn Ser Glu Glu Cys Pro Gly 595 600 605 Thr Tyr Glu Asp Phe Arg Ala Gln Gln Cys Ala Lys Arg Asn Ser Tyr 610 615 620 Tyr Val His Gln Asn Ala Lys His Ser Trp Val Pro Tyr Glu Pro Asp 625 630 635 640 Asp Asp Ala Gln Lys Cys Glu Leu Ile Cys Gln Ser Ala Asp Thr Gly 645 650 655 Asp Val Val Phe Met Asn Gln Val Val His Asp Gly Thr Arg Cys Ser 660 665 670 Tyr Arg Asp Pro Tyr Ser Val Cys Ala Arg Gly Glu Cys Val Pro Val 675 680 685 Gly Cys Asp Lys Glu Val Gly Ser Met Lys Ala Asp Asp Lys Cys Gly 690 695 700 Val Cys Gly Gly Asp Asn Ser His Cys Arg Thr Val Lys Gly Thr Leu 705 710 715 720 Gly Lys Ala Ser Lys Gln Ala Gly Ala Leu Lys Leu Val Gln Ile Pro 725 730 735 Ala Gly Ala Arg His Ile Gln Ile Glu Ala Leu Glu Lys Ser Pro His 740 745 750 Arg Ser Val Val Lys Asn Gln Val Thr Gly Ser Phe Ile Leu Asn Pro 755 760 765 Lys Gly Lys Glu Ala Thr Ser Arg Thr Phe Thr Ala Met Gly Leu Glu 770 775 780 Trp Glu Asp Ala Val Glu Asp Ala Lys Glu Ser Leu Lys Thr Ser Gly 785 790 795 800 Pro Leu Pro Glu Ala Ile Ala Ile Leu Ala Leu Pro Pro Thr Glu Gly 805 810 815 Gly Pro Arg Ser Ser Leu Ala Tyr Lys Tyr Val Ile His Glu Asp Leu 820 825 830 Leu Pro Leu Ile Gly Ser Asn Asn Val Leu Leu Glu Glu Met Asp Thr 835 840 845 Tyr Glu Trp Ala Leu Lys Ser Trp Ala Pro Cys Ser Lys Ala Cys Gly 850 855 860 Gly Gly Ile Gln Phe Thr Lys Tyr Gly Cys Arg Arg Arg Arg Asp His 865 870 875 880 His Met Val Gln Arg His Leu Cys Asp His Lys Lys Arg Pro Lys Pro 885 890 895 Ile Arg Arg Arg Cys Asn Gln His Pro Cys Ser Gln Pro Val Trp Val 900 905 910 Thr Glu Glu Trp Gly Ala Cys Ser Arg Ser Cys Gly Lys Leu Gly Val 915 920 925 Gln Thr Arg Gly Ile Gln Cys Leu Leu Pro Leu Ser Asn Gly Thr His 930 935 940 Lys Val Met Pro Ala Lys Ala Cys Ala Gly Asp Arg Pro Glu Ala Arg 945 950 955 960 Arg Pro Cys Leu Arg Val Pro Cys Pro Ala Gln Trp Arg Leu Gly Ala 965 970 975 Trp Ser Gln Cys Ser Ala Thr Cys Gly Glu Gly Ile Gln Gln Arg Gln 980 985 990 Val Val Cys Arg Thr Asn Ala Asn Ser Leu Gly His Cys Glu Gly Asp 995 1000 1005 Arg Pro Asp Thr Val Gln Val Cys Ser Leu Pro Ala Cys Gly Gly Asn 1010 1015 1020 His Gln Asn Ser Thr Val Arg Ala Asp Val Trp Glu Leu Gly Thr Pro 1025 1030 1035 1040 Glu Gly Gln Trp Val Pro Gln Ser Gly Pro Leu His Pro Ile Asn Lys 1045 1050 1055 Ile Ser Ser Thr Glu Pro Cys Thr Gly Asp Arg Ser Val Phe Cys Gln 1060 1065 1070 Met Glu Val Leu Asp Arg Tyr Cys Ser Ile Pro Gly Tyr His Arg Leu 1075 1080 1085 Cys Cys Val Ser Cys Ile Lys Lys Ala Ser Gly Pro Asn Pro Gly Pro 1090 1095 1100 Asp Pro Gly Pro Thr Ser Leu Pro Pro Phe Ser Thr Pro Gly Ser Pro 1105 1110 1115 1120 Leu Pro Gly Pro Gln Asp Pro Ala Asp Ala Ala Glu Pro Pro Gly Lys 1125 1130 1135 Pro Thr Gly Ser Glu Asp His Gln His Gly Arg Ala Thr Gln Leu Pro 1140 1145 1150 Gly Ala Leu Asp Thr Ser Ser Pro Gly Thr Gln His Pro Phe Ala Pro 1155 1160 1165 Glu Thr Pro Ile Pro Gly Ala Ser Trp Ser Ile Ser Pro Thr Thr Pro 1170 1175 1180 Gly Gly Leu Pro Trp Gly Trp Thr Gln Thr Pro Thr Pro Val Pro Glu 1185 1190 1195 1200 Asp Lys Gly Gln Pro Gly Glu Asp Leu Arg His Pro Gly Thr Ser Leu 1205 1210 1215 Pro Ala Asp Leu Pro Gly Arg Pro Pro Glu Pro Tyr Ser Glu Ser Asp 1220 1225 1230 19 3759 DNA homo sapiens 19 atggctccac tccgcgcgct gctgtcctac ctgctgcctt tgcactgtgc gctctgcrcc 60 gccgcgggca gccggacccc agagctgcac ctctctggaa agctcagtga ctatggtgtg 120 acagtgccct gcagcacaga ctttcgggga cgcttcctct cccacgtggt gtctggccca 180 gcagcagcct ctgcagggag catggtagtg gacacgccac ccacactacc acgacactcc 240 agtcacctcc gggtggctcg cagccctctg cacccaggag ggaccctgtg gcctggcagg 300 gtggggcgcc actccctcta cttcaatgtc actgttttcg ggaaggaact gcacttgcgc 360 ctgcggccca atcggaggtt ggtagtgcca ggatcctcag tggagtggca ggaggatttt 420 cgggagctgt tccggcagcc cttacggcag gagtgtgtgt acactggagg tgtcactgga 480 atgcctgggg cagctgttgc catcagcaac tgtgacggat tggcgggcct catccgcaca 540 gacagcaccg acttcttcat tgagcctctg gagcggggcc agcaggagaa ggaggccagc 600 gggaggacac atgtggtgta ccgccgggag gccgtccagc aggagtgggc agaacctgac 660 ggggacctgc acaatgaagc ctttggcctg ggagaccttc ccaacctgct gggcctggtg 720 ggggaccagc tgggcgacac agagcggaag cggcggcatg ccaagccagg cagctacagc 780 atcgaggtgc tgctggtggt ggacgactcg gtggttcgct tccatggcaa ggagcatgtg 840 cagaactatg tcctcaccct catgaatatc gtagatgaga tttaccacga tgagtccctg 900 ggggttcata taaatattgc cctcgtccgc ttgatcatgg ttggctaccg acagtccctg 960 agcctgatcg agcgcgggaa cccctcacgc agcctggagc aggtgtgtcg ctgggcacac 1020 tcccagcagc gccaggaccc cagccacgct gagcaccatg accacgttgt gttcctcacc 1080 cggcaggact ttgggccctc agggtatgca cccgtcactg gcatgtgtca ccccctgagg 1140 agctgtgccc tcaaccatga ggatggcttc tcctcagcct tcgtgatagc tcatgagacc 1200 ggccacgtgc tcggcatgga gcatgacggt caggggaatg gctgtgcaga tgagaccagc 1260 ctgggcagcg tcatggcgcc cctggtgcag gctgccttcc accgcttcca ttggtcccgc 1320 tgcagcaagc tggagctcag ccgctacctc ccctcctacg actgcctcct cgatgacccc 1380 tttgatcctg cctggcccca gcccccagag ctgcctggga tcaactactc aatggatgag 1440 cagtgccgct ttgactttgg cagtggctac cagacctgct tggcattcag gacctttgag 1500 ccctgcaagc agctgtggtg cagccatcct gacaaccmgt ayttctgcaa gaccaagaag 1560 gggcccccgc tggatgggac tgagtgtgca cccggcaagt ggtgcttcaa aggtcactgc 1620 atctggaagt cgccggagca gacatatggc caggatggag gctggagctc ctggaccaag 1680 tttgggtcat gttcgcggtc atgtgggggc ggggtgcgat cccgcagccg gagctgcaac 1740 aacccctccc cagcctatgg aggccgccyg tgcttagggc ccatgttcga gtaccaggtc 1800 tgcaacagcg aggagtgccc tgggacctac gaggacttcc gggcccagca gtgtgccaag 1860 cgcaactcst actatgtgca ccagaatgcc aagcacagst gggtgcccta cgagcctgac 1920 gatgacgccc agaagtgtga gctgatctgc cagtcggcgg acacrgggga cgtggtgttc 1980 atgaaccagg tggttcacga tgggacacgc tgcagctacc gggacccata cagcgtctgt 2040 gcgcgtggcg agtgtgtgcc tgtcggctgt gacaaggagg tggggtccat gaaggcggat 2100 gacaagtgtg gagtctgcgg gggtgacaac tcccactgca ggactgtgaa ggggacgctg 2160 ggcaaggcct ccaagcaggc aggagctctc aagctggtgc agatcccagc aggtgccagg 2220 cacatccaga ttgaggcact ggagaagtcc ccccaccgsw ywgtggtgaa gaaccaggtc 2280 accggcagct tcatcctcaa ccccaagggc aaggaagcca caagccggac cttcaccgcc 2340 atgggcctgg agtgggagga tgcggtggag gatgccaagg aaagcctcaa gaccagcggg 2400 cccctgcctg aagccattgc catcctggct ctccccccaa ctgagggtgg cccccgcagc 2460 agcctggcct acaagtacgt catccatgag gacctgctgc cccttatcgg gagcaacaat 2520 gtgctcctgg aggagatgga cacctatgag tgggcgctca agagctgggc cccctgcagc 2580 aaggcctgtg gaggagggat ccagttcacc aaatacggct gccggcgcag acgagaccac 2640 cacatggtgc agcgacacct gtgtgaccac aagaagaggc ccaagcccat ccgccggcgc 2700 tgcaaccagc acccgtgctc tcagcctgtg tgggtgacgg aggagtgggg tgcctgcagc 2760 cggagctgtg ggaagctggg ggtgcagaca cgggggatac agtgcctgct gcccctctcc 2820 aatggaaccc acaaggtcat gccggccaaa gcctgcgccg gggaccggcc tgaggcccga 2880 cggccctgtc tccgagtgcc ctgcccagcc cagtggaggc tgggagcctg gtcccagtgc 2940 tctgccacct gtggagaggg catccagcag cggcaggtgg tgtgcaggac caacgccaac 3000 agcctcgggc attgcgaggg ggataggcca gacactgtcc aggtctgcar cctgcccgcc 3060 tgtggaggaa atcaccagaa ctccacggtg agggccgatg tctgggaact tgggacgcca 3120 gaggggcagt gggtgccaca atctgraccc ctacatccca ttaacaagat atcatcaatg 3180 tgtgcagcgg agccctgcac gggagacagg tctgtcttct gccagatgga agtgctcgat 3240 cgctactgct ccattcccgg ctaccaccgg ctctgctgtg tgtcctgcat caagaaggcc 3300 tcgggcccca accctggccc agaccctggc ccaacctcac tgcccccctt ctccactcct 3360 ggaagcccct taccaggacc ccaggaccct gcagatgctg cagagcctcc tggaaagcca 3420 acgggatcag aggaccatca gcatggccga gccacacagc tcccaggagc tctggataca 3480 agctccccag ggacccagca tccctttgcc cctgagacac caatccctgg agcatcctgg 3540 agcatctccc ctaccacccc cggggggctg ccttggggct ggactcagac acctacgcca 3600 gtccctgagg acaaagggca acctggagaa gacctgagac atcccggcac cagcctccct 3660 gctgacctgc ccgggcggcc gcccgagccc tgccatccca ctggcacgtt tacactctgt 3720 gtactgcccc gtgactccca gctcagagga cacacatag 3759 20 1252 PRT homo sapiens 20 Met Ala Pro Leu Arg Ala Leu Leu Ser Tyr Leu Leu Pro Leu His Cys 1 5 10 15 Ala Leu Cys Thr Ala Ala Gly Ser Arg Thr Pro Glu Leu His Leu Ser 20 25 30 Gly Lys Leu Ser Asp Tyr Gly Val Thr Val Pro Cys Ser Thr Asp Phe 35 40 45 Arg Gly Arg Phe Leu Ser His Val Val Ser Gly Pro Ala Ala Ala Ser 50 55 60 Ala Gly Ser Met Val Val Asp Thr Pro Pro Thr Leu Pro Arg His Ser 65 70 75 80 Ser His Leu Arg Val Ala Arg Ser Pro Leu His Pro Gly Gly Thr Leu 85 90 95 Trp Pro Gly Arg Val Gly Arg His Ser Leu Tyr Phe Asn Val Thr Val 100 105 110 Phe Gly Lys Glu Leu His Leu Arg Leu Arg Pro Asn Arg Arg Leu Val 115 120 125 Val Pro Gly Ser Ser Val Glu Trp Gln Glu Asp Phe Arg Glu Leu Phe 130 135 140 Arg Gln Pro Leu Arg Gln Glu Cys Val Tyr Thr Gly Gly Val Thr Gly 145 150 155 160 Met Pro Gly Ala Ala Val Ala Ile Ser Asn Cys Asp Gly Leu Ala Gly 165 170 175 Leu Ile Arg Thr Asp Ser Thr Asp Phe Phe Ile Glu Pro Leu Glu Arg 180 185 190 Gly Gln Gln Glu Lys Glu Ala Ser Gly Arg Thr His Val Val Tyr Arg 195 200 205 Arg Glu Ala Val Gln Gln Glu Trp Ala Glu Pro Asp Gly Asp Leu His 210 215 220 Asn Glu Ala Phe Gly Leu Gly Asp Leu Pro Asn Leu Leu Gly Leu Val 225 230 235 240 Gly Asp Gln Leu Gly Asp Thr Glu Arg Lys Arg Arg His Ala Lys Pro 245 250 255 Gly Ser Tyr Ser Ile Glu Val Leu Leu Val Val Asp Asp Ser Val Val 260 265 270 Arg Phe His Gly Lys Glu His Val Gln Asn Tyr Val Leu Thr Leu Met 275 280 285 Asn Ile Val Asp Glu Ile Tyr His Asp Glu Ser Leu Gly Val His Ile 290 295 300 Asn Ile Ala Leu Val Arg Leu Ile Met Val Gly Tyr Arg Gln Ser Leu 305 310 315 320 Ser Leu Ile Glu Arg Gly Asn Pro Ser Arg Ser Leu Glu Gln Val Cys 325 330 335 Arg Trp Ala His Ser Gln Gln Arg Gln Asp Pro Ser His Ala Glu His 340 345 350 His Asp His Val Val Phe Leu Thr Arg Gln Asp Phe Gly Pro Ser Gly 355 360 365 Tyr Ala Pro Val Thr Gly Met Cys His Pro Leu Arg Ser Cys Ala Leu 370 375 380 Asn His Glu Asp Gly Phe Ser Ser Ala Phe Val Ile Ala His Glu Thr 385 390 395 400 Gly His Val Leu Gly Met Glu His Asp Gly Gln Gly Asn Gly Cys Ala 405 410 415 Asp Glu Thr Ser Leu Gly Ser Val Met Ala Pro Leu Val Gln Ala Ala 420 425 430 Phe His Arg Phe His Trp Ser Arg Cys Ser Lys Leu Glu Leu Ser Arg 435 440 445 Tyr Leu Pro Ser Tyr Asp Cys Leu Leu Asp Asp Pro Phe Asp Pro Ala 450 455 460 Trp Pro Gln Pro Pro Glu Leu Pro Gly Ile Asn Tyr Ser Met Asp Glu 465 470 475 480 Gln Cys Arg Phe Asp Phe Gly Ser Gly Tyr Gln Thr Cys Leu Ala Phe 485 490 495 Arg Thr Phe Glu Pro Cys Lys Gln Leu Trp Cys Ser His Pro Asp Asn 500 505 510 Pro Tyr Phe Cys Lys Thr Lys Lys Gly Pro Pro Leu Asp Gly Thr Glu 515 520 525 Cys Ala Pro Gly Lys Trp Cys Phe Lys Gly His Cys Ile Trp Lys Ser 530 535 540 Pro Glu Gln Thr Tyr Gly Gln Asp Gly Gly Trp Ser Ser Trp Thr Lys 545 550 555 560 Phe Gly Ser Cys Ser Arg Ser Cys Gly Gly Gly Val Arg Ser Arg Ser 565 570 575 Arg Ser Cys Asn Asn Pro Ser Pro Ala Tyr Gly Gly Arg Pro Cys Leu 580 585 590 Gly Pro Met Phe Glu Tyr Gln Val Cys Asn Ser Glu Glu Cys Pro Gly 595 600 605 Thr Tyr Glu Asp Phe Arg Ala Gln Gln Cys Ala Lys Arg Asn Ser Tyr 610 615 620 Tyr Val His Gln Asn Ala Lys His Ser Trp Val Pro Tyr Glu Pro Asp 625 630 635 640 Asp Asp Ala Gln Lys Cys Glu Leu Ile Cys Gln Ser Ala Asp Thr Gly 645 650 655 Asp Val Val Phe Met Asn Gln Val Val His Asp Gly Thr Arg Cys Ser 660 665 670 Tyr Arg Asp Pro Tyr Ser Val Cys Ala Arg Gly Glu Cys Val Pro Val 675 680 685 Gly Cys Asp Lys Glu Val Gly Ser Met Lys Ala Asp Asp Lys Cys Gly 690 695 700 Val Cys Gly Gly Asp Asn Ser His Cys Arg Thr Val Lys Gly Thr Leu 705 710 715 720 Gly Lys Ala Ser Lys Gln Ala Gly Ala Leu Lys Leu Val Gln Ile Pro 725 730 735 Ala Gly Ala Arg His Ile Gln Ile Glu Ala Leu Glu Lys Ser Pro His 740 745 750 Arg Ser Val Val Lys Asn Gln Val Thr Gly Ser Phe Ile Leu Asn Pro 755 760 765 Lys Gly Lys Glu Ala Thr Ser Arg Thr Phe Thr Ala Met Gly Leu Glu 770 775 780 Trp Glu Asp Ala Val Glu Asp Ala Lys Glu Ser Leu Lys Thr Ser Gly 785 790 795 800 Pro Leu Pro Glu Ala Ile Ala Ile Leu Ala Leu Pro Pro Thr Glu Gly 805 810 815 Gly Pro Arg Ser Ser Leu Ala Tyr Lys Tyr Val Ile His Glu Asp Leu 820 825 830 Leu Pro Leu Ile Gly Ser Asn Asn Val Leu Leu Glu Glu Met Asp Thr 835 840 845 Tyr Glu Trp Ala Leu Lys Ser Trp Ala Pro Cys Ser Lys Ala Cys Gly 850 855 860 Gly Gly Ile Gln Phe Thr Lys Tyr Gly Cys Arg Arg Arg Arg Asp His 865 870 875 880 His Met Val Gln Arg His Leu Cys Asp His Lys Lys Arg Pro Lys Pro 885 890 895 Ile Arg Arg Arg Cys Asn Gln His Pro Cys Ser Gln Pro Val Trp Val 900 905 910 Thr Glu Glu Trp Gly Ala Cys Ser Arg Ser Cys Gly Lys Leu Gly Val 915 920 925 Gln Thr Arg Gly Ile Gln Cys Leu Leu Pro Leu Ser Asn Gly Thr His 930 935 940 Lys Val Met Pro Ala Lys Ala Cys Ala Gly Asp Arg Pro Glu Ala Arg 945 950 955 960 Arg Pro Cys Leu Arg Val Pro Cys Pro Ala Gln Trp Arg Leu Gly Ala 965 970 975 Trp Ser Gln Cys Ser Ala Thr Cys Gly Glu Gly Ile Gln Gln Arg Gln 980 985 990 Val Val Cys Arg Thr Asn Ala Asn Ser Leu Gly His Cys Glu Gly Asp 995 1000 1005 Arg Pro Asp Thr Val Gln Val Cys Ser Leu Pro Ala Cys Gly Gly Asn 1010 1015 1020 His Gln Asn Ser Thr Val Arg Ala Asp Val Trp Glu Leu Gly Thr Pro 1025 1030 1035 1040 Glu Gly Gln Trp Val Pro Gln Ser Gly Pro Leu His Pro Ile Asn Lys 1045 1050 1055 Ile Ser Ser Met Cys Ala Ala Glu Pro Cys Thr Gly Asp Arg Ser Val 1060 1065 1070 Phe Cys Gln Met Glu Val Leu Asp Arg Tyr Cys Ser Ile Pro Gly Tyr 1075 1080 1085 His Arg Leu Cys Cys Val Ser Cys Ile Lys Lys Ala Ser Gly Pro Asn 1090 1095 1100 Pro Gly Pro Asp Pro Gly Pro Thr Ser Leu Pro Pro Phe Ser Thr Pro 1105 1110 1115 1120 Gly Ser Pro Leu Pro Gly Pro Gln Asp Pro Ala Asp Ala Ala Glu Pro 1125 1130 1135 Pro Gly Lys Pro Thr Gly Ser Glu Asp His Gln His Gly Arg Ala Thr 1140 1145 1150 Gln Leu Pro Gly Ala Leu Asp Thr Ser Ser Pro Gly Thr Gln His Pro 1155 1160 1165 Phe Ala Pro Glu Thr Pro Ile Pro Gly Ala Ser Trp Ser Ile Ser Pro 1170 1175 1180 Thr Thr Pro Gly Gly Leu Pro Trp Gly Trp Thr Gln Thr Pro Thr Pro 1185 1190 1195 1200 Val Pro Glu Asp Lys Gly Gln Pro Gly Glu Asp Leu Arg His Pro Gly 1205 1210 1215 Thr Ser Leu Pro Ala Asp Leu Pro Gly Arg Pro Pro Glu Pro Cys His 1220 1225 1230 Pro Thr Gly Thr Phe Thr Leu Cys Val Leu Pro Arg Asp Ser Gln Leu 1235 1240 1245 Arg Gly His Thr 1250 21 3750 DNA homo sapiens 21 atggctccac tccgcgcgct gctgtcctac ctgctgcctt tgcactgtgc gctctgcrcc 60 gccgcgggca gccggacccc agagctgcac ctctctggaa agctcagtga ctatggtgtg 120 acagtgccct gcagcacaga ctttcgggga cgcttcctct cccacgtggt gtctggccca 180 gcagcagcct ctgcagggag catggtagtg gacacgccac ccacactacc acgacactcc 240 agtcacctcc gggtggctcg cagccctctg cacccaggag ggaccctgtg gcctggcagg 300 gtggggcgcc actccctcta cttcaatgtc actgttttcg ggaaggaact gcacttgcgc 360 ctgcggccca atcggaggtt ggtagtgcca ggatcctcag tggagtggca ggaggatttt 420 cgggagctgt tccggcagcc cttacggcag gagtgtgtgt acactggagg tgtcactgga 480 atgcctgggg cagctgttgc catcagcaac tgtgacggat tggcgggcct catccgcaca 540 gacagcaccg acttcttcat tgagcctctg gagcggggcc agcaggagaa ggaggccagc 600 gggaggacac atgtggtgta ccgccgggag gccgtccagc aggagtgggc agaacctgac 660 ggggacctgc acaatgaagc ctttggcctg ggagaccttc ccaacctgct gggcctggtg 720 ggggaccagc tgggcgacac agagcggaag cggcggcatg ccaagccagg cagctacagc 780 atcgaggtgc tgctggtggt ggacgactcg gtggttcgct tccatggcaa ggagcatgtg 840 cagaactatg tcctcaccct catgaatatc gtagatgaga tttaccacga tgagtccctg 900 ggggttcata taaatattgc cctcgtccgc ttgatcatgg ttggctaccg acagtccctg 960 agcctgatcg agcgcgggaa cccctcacgc agcctggagc aggtgtgtcg ctgggcacac 1020 tcccagcagc gccaggaccc cagccacgct gagcaccatg accacgttgt gttcctcacc 1080 cggcaggact ttgggccctc agggtatgca cccgtcactg gcatgtgtca ccccctgagg 1140 agctgtgccc tcaaccatga ggatggcttc tcctcagcct tcgtgatagc tcatgagacc 1200 ggccacgtgc tcggcatgga gcatgacggt caggggaatg gctgtgcaga tgagaccagc 1260 ctgggcagcg tcatggcgcc cctggtgcag gctgccttcc accgcttcca ttggtcccgc 1320 tgcagcaagc tggagctcag ccgctacctc ccctcctacg actgcctcct cgatgacccc 1380 tttgatcctg cctggcccca gcccccagag ctgcctggga tcaactactc aatggatgag 1440 cagtgccgct ttgactttgg cagtggctac cagacctgct tggcattcag gacctttgag 1500 ccctgcaagc agctgtggtg cagccatcct gacaaccmgt ayttctgcaa gaccaagaag 1560 gggcccccgc tggatgggac tgagtgtgca cccggcaagt ggtgcttcaa aggtcactgc 1620 atctggaagt cgccggagca gacatatggc caggatggag gctggagctc ctggaccaag 1680 tttgggtcat gttcgcggtc atgtgggggc ggggtgcgat cccgcagccg gagctgcaac 1740 aacccctccc cagcctatgg aggccgccyg tgcttagggc ccatgttcga gtaccaggtc 1800 tgcaacagcg aggagtgccc tgggacctac gaggacttcc gggcccagca gtgtgccaag 1860 cgcaactcst actatgtgca ccagaatgcc aagcacagst gggtgcccta cgagcctgac 1920 gatgacgccc agaagtgtga gctgatctgc cagtcggcgg acacrgggga cgtggtgttc 1980 atgaaccagg tggttcacga tgggacacgc tgcagctacc gggacccata cagcgtctgt 2040 gcgcgtggcg agtgtgtgcc tgtcggctgt gacaaggagg tggggtccat gaaggcggat 2100 gacaagtgtg gagtctgcgg gggtgacaac tcccactgca ggactgtgaa ggggacgctg 2160 ggcaaggcct ccaagcaggc aggagctctc aagctggtgc agatcccagc aggtgccagg 2220 cacatccaga ttgaggcact ggagaagtcc ccccaccgsw ywgtggtgaa gaaccaggtc 2280 accggcagct tcatcctcaa ccccaagggc aaggaagcca caagccggac cttcaccgcc 2340 atgggcctgg agtgggagga tgcggtggag gatgccaagg aaagcctcaa gaccagcggg 2400 cccctgcctg aagccattgc catcctggct ctccccccaa ctgagggtgg cccccgcagc 2460 agcctggcct acaagtacgt catccatgag gacctgctgc cccttatcgg gagcaacaat 2520 gtgctcctgg aggagatgga cacctatgag tgggcgctca agagctgggc cccctgcagc 2580 aaggcctgtg gaggagggat ccagttcacc aaatacggct gccggcgcag acgagaccac 2640 cacatggtgc agcgacacct gtgtgaccac aagaagaggc ccaagcccat ccgccggcgc 2700 tgcaaccagc acccgtgctc tcagcctgtg tgggtgacgg aggagtgggg tgcctgcagc 2760 cggagctgtg ggaagctggg ggtgcagaca cgggggatac agtgcctgct gcccctctcc 2820 aatggaaccc acaaggtcat gccggccaaa gcctgcgccg gggaccggcc tgaggcccga 2880 cggccctgtc tccgagtgcc ctgcccagcc cagtggaggc tgggagcctg gtcccagtgc 2940 tctgccacct gtggagaggg catccagcag cggcaggtgg tgtgcaggac caacgccaac 3000 agcctcgggc attgcgaggg ggataggcca gacactgtcc aggtctgcar cctgcccgcc 3060 tgtggaggaa atcaccagaa ctccacggtg agggccgatg tctgggaact tgggacgcca 3120 gaggggcagt gggtgccaca atctgraccc ctacatccca ttaacaagat atcatcaacg 3180 gagccctgca cgggagacag gtctgtcttc tgccagatgg aagtgctcga tcgctactgc 3240 tccattcccg gctaccaccg gctctgctgt gtgtcctgca tcaagaaggc ctcgggcccc 3300 aaccctggcc cagaccctgg cccaacctca ctgcccccct tctccactcc tggaagcccc 3360 ttaccaggac cccaggaccc tgcagatgct gcagagcctc ctggaaagcc aacgggatca 3420 gaggaccatc agcatggccg agccacacag ctcccaggag ctctggatac aagctcccca 3480 gggacccagc atccctttgc ccctgagaca ccaatccctg gagcatcctg gagcatctcc 3540 cctaccaccc ccggggggct gccttggggc tggactcaga cacctacgcc agtccctgag 3600 gacaaagggc aacctggaga agacctgaga catcccggca ccagcctccc tgctgacctg 3660 cccgggcggc cgcccgagcc ctgccatccc actggcacgt ttacactctg tgtactgccc 3720 cgtgactccc agctcagagg acacacatag 3750 22 1249 PRT homo sapiens 22 Met Ala Pro Leu Arg Ala Leu Leu Ser Tyr Leu Leu Pro Leu His Cys 1 5 10 15 Ala Leu Cys Thr Ala Ala Gly Ser Arg Thr Pro Glu Leu His Leu Ser 20 25 30 Gly Lys Leu Ser Asp Tyr Gly Val Thr Val Pro Cys Ser Thr Asp Phe 35 40 45 Arg Gly Arg Phe Leu Ser His Val Val Ser Gly Pro Ala Ala Ala Ser 50 55 60 Ala Gly Ser Met Val Val Asp Thr Pro Pro Thr Leu Pro Arg His Ser 65 70 75 80 Ser His Leu Arg Val Ala Arg Ser Pro Leu His Pro Gly Gly Thr Leu 85 90 95 Trp Pro Gly Arg Val Gly Arg His Ser Leu Tyr Phe Asn Val Thr Val 100 105 110 Phe Gly Lys Glu Leu His Leu Arg Leu Arg Pro Asn Arg Arg Leu Val 115 120 125 Val Pro Gly Ser Ser Val Glu Trp Gln Glu Asp Phe Arg Glu Leu Phe 130 135 140 Arg Gln Pro Leu Arg Gln Glu Cys Val Tyr Thr Gly Gly Val Thr Gly 145 150 155 160 Met Pro Gly Ala Ala Val Ala Ile Ser Asn Cys Asp Gly Leu Ala Gly 165 170 175 Leu Ile Arg Thr Asp Ser Thr Asp Phe Phe Ile Glu Pro Leu Glu Arg 180 185 190 Gly Gln Gln Glu Lys Glu Ala Ser Gly Arg Thr His Val Val Tyr Arg 195 200 205 Arg Glu Ala Val Gln Gln Glu Trp Ala Glu Pro Asp Gly Asp Leu His 210 215 220 Asn Glu Ala Phe Gly Leu Gly Asp Leu Pro Asn Leu Leu Gly Leu Val 225 230 235 240 Gly Asp Gln Leu Gly Asp Thr Glu Arg Lys Arg Arg His Ala Lys Pro 245 250 255 Gly Ser Tyr Ser Ile Glu Val Leu Leu Val Val Asp Asp Ser Val Val 260 265 270 Arg Phe His Gly Lys Glu His Val Gln Asn Tyr Val Leu Thr Leu Met 275 280 285 Asn Ile Val Asp Glu Ile Tyr His Asp Glu Ser Leu Gly Val His Ile 290 295 300 Asn Ile Ala Leu Val Arg Leu Ile Met Val Gly Tyr Arg Gln Ser Leu 305 310 315 320 Ser Leu Ile Glu Arg Gly Asn Pro Ser Arg Ser Leu Glu Gln Val Cys 325 330 335 Arg Trp Ala His Ser Gln Gln Arg Gln Asp Pro Ser His Ala Glu His 340 345 350 His Asp His Val Val Phe Leu Thr Arg Gln Asp Phe Gly Pro Ser Gly 355 360 365 Tyr Ala Pro Val Thr Gly Met Cys His Pro Leu Arg Ser Cys Ala Leu 370 375 380 Asn His Glu Asp Gly Phe Ser Ser Ala Phe Val Ile Ala His Glu Thr 385 390 395 400 Gly His Val Leu Gly Met Glu His Asp Gly Gln Gly Asn Gly Cys Ala 405 410 415 Asp Glu Thr Ser Leu Gly Ser Val Met Ala Pro Leu Val Gln Ala Ala 420 425 430 Phe His Arg Phe His Trp Ser Arg Cys Ser Lys Leu Glu Leu Ser Arg 435 440 445 Tyr Leu Pro Ser Tyr Asp Cys Leu Leu Asp Asp Pro Phe Asp Pro Ala 450 455 460 Trp Pro Gln Pro Pro Glu Leu Pro Gly Ile Asn Tyr Ser Met Asp Glu 465 470 475 480 Gln Cys Arg Phe Asp Phe Gly Ser Gly Tyr Gln Thr Cys Leu Ala Phe 485 490 495 Arg Thr Phe Glu Pro Cys Lys Gln Leu Trp Cys Ser His Pro Asp Asn 500 505 510 Pro Tyr Phe Cys Lys Thr Lys Lys Gly Pro Pro Leu Asp Gly Thr Glu 515 520 525 Cys Ala Pro Gly Lys Trp Cys Phe Lys Gly His Cys Ile Trp Lys Ser 530 535 540 Pro Glu Gln Thr Tyr Gly Gln Asp Gly Gly Trp Ser Ser Trp Thr Lys 545 550 555 560 Phe Gly Ser Cys Ser Arg Ser Cys Gly Gly Gly Val Arg Ser Arg Ser 565 570 575 Arg Ser Cys Asn Asn Pro Ser Pro Ala Tyr Gly Gly Arg Pro Cys Leu 580 585 590 Gly Pro Met Phe Glu Tyr Gln Val Cys Asn Ser Glu Glu Cys Pro Gly 595 600 605 Thr Tyr Glu Asp Phe Arg Ala Gln Gln Cys Ala Lys Arg Asn Ser Tyr 610 615 620 Tyr Val His Gln Asn Ala Lys His Ser Trp Val Pro Tyr Glu Pro Asp 625 630 635 640 Asp Asp Ala Gln Lys Cys Glu Leu Ile Cys Gln Ser Ala Asp Thr Gly 645 650 655 Asp Val Val Phe Met Asn Gln Val Val His Asp Gly Thr Arg Cys Ser 660 665 670 Tyr Arg Asp Pro Tyr Ser Val Cys Ala Arg Gly Glu Cys Val Pro Val 675 680 685 Gly Cys Asp Lys Glu Val Gly Ser Met Lys Ala Asp Asp Lys Cys Gly 690 695 700 Val Cys Gly Gly Asp Asn Ser His Cys Arg Thr Val Lys Gly Thr Leu 705 710 715 720 Gly Lys Ala Ser Lys Gln Ala Gly Ala Leu Lys Leu Val Gln Ile Pro 725 730 735 Ala Gly Ala Arg His Ile Gln Ile Glu Ala Leu Glu Lys Ser Pro His 740 745 750 Arg Ser Val Val Lys Asn Gln Val Thr Gly Ser Phe Ile Leu Asn Pro 755 760 765 Lys Gly Lys Glu Ala Thr Ser Arg Thr Phe Thr Ala Met Gly Leu Glu 770 775 780 Trp Glu Asp Ala Val Glu Asp Ala Lys Glu Ser Leu Lys Thr Ser Gly 785 790 795 800 Pro Leu Pro Glu Ala Ile Ala Ile Leu Ala Leu Pro Pro Thr Glu Gly 805 810 815 Gly Pro Arg Ser Ser Leu Ala Tyr Lys Tyr Val Ile His Glu Asp Leu 820 825 830 Leu Pro Leu Ile Gly Ser Asn Asn Val Leu Leu Glu Glu Met Asp Thr 835 840 845 Tyr Glu Trp Ala Leu Lys Ser Trp Ala Pro Cys Ser Lys Ala Cys Gly 850 855 860 Gly Gly Ile Gln Phe Thr Lys Tyr Gly Cys Arg Arg Arg Arg Asp His 865 870 875 880 His Met Val Gln Arg His Leu Cys Asp His Lys Lys Arg Pro Lys Pro 885 890 895 Ile Arg Arg Arg Cys Asn Gln His Pro Cys Ser Gln Pro Val Trp Val 900 905 910 Thr Glu Glu Trp Gly Ala Cys Ser Arg Ser Cys Gly Lys Leu Gly Val 915 920 925 Gln Thr Arg Gly Ile Gln Cys Leu Leu Pro Leu Ser Asn Gly Thr His 930 935 940 Lys Val Met Pro Ala Lys Ala Cys Ala Gly Asp Arg Pro Glu Ala Arg 945 950 955 960 Arg Pro Cys Leu Arg Val Pro Cys Pro Ala Gln Trp Arg Leu Gly Ala 965 970 975 Trp Ser Gln Cys Ser Ala Thr Cys Gly Glu Gly Ile Gln Gln Arg Gln 980 985 990 Val Val Cys Arg Thr Asn Ala Asn Ser Leu Gly His Cys Glu Gly Asp 995 1000 1005 Arg Pro Asp Thr Val Gln Val Cys Ser Leu Pro Ala Cys Gly Gly Asn 1010 1015 1020 His Gln Asn Ser Thr Val Arg Ala Asp Val Trp Glu Leu Gly Thr Pro 1025 1030 1035 1040 Glu Gly Gln Trp Val Pro Gln Ser Gly Pro Leu His Pro Ile Asn Lys 1045 1050 1055 Ile Ser Ser Thr Glu Pro Cys Thr Gly Asp Arg Ser Val Phe Cys Gln 1060 1065 1070 Met Glu Val Leu Asp Arg Tyr Cys Ser Ile Pro Gly Tyr His Arg Leu 1075 1080 1085 Cys Cys Val Ser Cys Ile Lys Lys Ala Ser Gly Pro Asn Pro Gly Pro 1090 1095 1100 Asp Pro Gly Pro Thr Ser Leu Pro Pro Phe Ser Thr Pro Gly Ser Pro 1105 1110 1115 1120 Leu Pro Gly Pro Gln Asp Pro Ala Asp Ala Ala Glu Pro Pro Gly Lys 1125 1130 1135 Pro Thr Gly Ser Glu Asp His Gln His Gly Arg Ala Thr Gln Leu Pro 1140 1145 1150 Gly Ala Leu Asp Thr Ser Ser Pro Gly Thr Gln His Pro Phe Ala Pro 1155 1160 1165 Glu Thr Pro Ile Pro Gly Ala Ser Trp Ser Ile Ser Pro Thr Thr Pro 1170 1175 1180 Gly Gly Leu Pro Trp Gly Trp Thr Gln Thr Pro Thr Pro Val Pro Glu 1185 1190 1195 1200 Asp Lys Gly Gln Pro Gly Glu Asp Leu Arg His Pro Gly Thr Ser Leu 1205 1210 1215 Pro Ala Asp Leu Pro Gly Arg Pro Pro Glu Pro Cys His Pro Thr Gly 1220 1225 1230 Thr Phe Thr Leu Cys Val Leu Pro Arg Asp Ser Gln Leu Arg Gly His 1235 1240 1245 Thr 23 4277 DNA homo sapiens 23 cagcggtcca ggcggcggcg ccgcgcaggg gacccggagc aggcgggagg gaagcagcta 60 ggcggggagg cggctgaggc ggcagcggcg gcagccagcc ggtgctccga cagcccgggg 120 cgcaccctag cctcgccgcc ctcagcctgg gacttgggga tcgggcgctt gcccagcccg 180 cgtcccagcg cggccacatg gctccactcc gcgcgctgct gtcctacctg ctgcctttgc 240 actgtgcgct ctgcrccgcc gcgggcagcc ggaccccaga gctgcacctc tctggaaagc 300 tcagtgacta tggtgtgaca gtgccctgca gcacagactt tcggggacgc ttcctctccc 360 acgtggtgtc tggcccagca gcagcctctg cagggagcat ggtagtggac acgccaccca 420 cactaccacg acactccagt cacctccggg tggctcgcag ccctctgcac ccaggaggga 480 ccctgtggcc tggcagggtg gggcgccact ccctctactt caatgtcact gttttcggga 540 aggaactgca cttgcgcctg cggcccaatc ggaggttggt agtgccagga tcctcagtgg 600 agtggcagga ggattttcgg gagctgttcc ggcagccctt acggcaggag tgtgtgtaca 660 ctggaggtgt cactggaatg cctggggcag ctgttgccat cagcaactgt gacggattgg 720 cgggcctcat ccgcacagac agcaccgact tcttcattga gcctctggag cggggccagc 780 aggagaagga ggccagcggg aggacacatg tggtgtaccg ccgggaggcc gtccagcagg 840 agtgggcaga acctgacggg gacctgcaca atgaagcctt tggcctggga gaccttccca 900 acctgctggg cctggtgggg gaccagctgg gcgacacaga gcggaagcgg cggcatgcca 960 agccaggcag ctacagcatc gaggtgctgc tggtggtgga cgactcggtg gttcgcttcc 1020 atggcaagga gcatgtgcag aactatgtcc tcaccctcat gaatatcgta gatgagattt 1080 accacgatga gtccctgggg gttcatataa atattgccct cgtccgcttg atcatggttg 1140 gctaccgaca gtccctgagc ctgatcgagc gcgggaaccc ctcacgcagc ctggagcagg 1200 tgtgtcgctg ggcacactcc cagcagcgcc aggaccccag ccacgctgag caccatgacc 1260 acgttgtgtt cctcacccgg caggactttg ggccctcagg gtatgcaccc gtcactggca 1320 tgtgtcaccc cctgaggagc tgtgccctca accatgagga tggcttctcc tcagccttcg 1380 tgatagctca tgagaccggc cacgtgctcg gcatggagca tgacggtcag gggaatggct 1440 gtgcagatga gaccagcctg ggcagcgtca tggcgcccct ggtgcaggct gccttccacc 1500 gcttccattg gtcccgctgc agcaagctgg agctcagccg ctacctcccc tcctacgact 1560 gcctcctcga tgaccccttt gatcctgcct ggccccagcc cccagagctg cctgggatca 1620 actactcaat ggatgagcag tgccgctttg actttggcag tggctaccag acctgcttgg 1680 cattcaggac ctttgagccc tgcaagcagc tgtggtgcag ccatcctgac aaccmgtayt 1740 tctgcaagac caagaagggg cccccgctgg atgggactga gtgtgcaccc ggcaagtggt 1800 gcttcaaagg tcactgcatc tggaagtcgc cggagcagac atatggccag gatggaggct 1860 ggagctcctg gaccaagttt gggtcatgtt cgcggtcatg tgggggcggg gtgcgatccc 1920 gcagccggag ctgcaacaac ccctccccag cctatggagg ccgccygtgc ttagggccca 1980 tgttcgagta ccaggtctgc aacagcgagg agtgccctgg gacctacgag gacttccggg 2040 cccagcagtg tgccaagcgc aactcstact atgtgcacca gaatgccaag cacagstggg 2100 tgccctacga gcctgacgat gacgcccaga agtgtgagct gatctgccag tcggcggaca 2160 crggggacgt ggtgttcatg aaccaggtgg ttcacgatgg gacacgctgc agctaccggg 2220 acccatacag cgtctgtgcg cgtggcgagt gtgtgcctgt cggctgtgac aaggaggtgg 2280 ggtccatgaa ggcggatgac aagtgtggag tctgcggggg tgacaactcc cactgcagga 2340 ctgtgaaggg gacgctgggc aaggcctcca agcaggcagg agctctcaag ctggtgcaga 2400 tcccagcagg tgccaggcac atccagattg aggcactgga gaagtccccc caccgswywg 2460 tggtgaagaa ccaggtcacc ggcagcttca tcctcaaccc caagggcaag gaagccacaa 2520 gccggacctt caccgccatg ggcctggagt gggaggatgc ggtggaggat gccaaggaaa 2580 gcctcaagac cagcgggccc ctgcctgaag ccattgccat cctggctctc cccccaactg 2640 agggtggccc ccgcagcagc ctggcctaca agtacgtcat ccatgaggac ctgctgcccc 2700 ttatcgggag caacaatgtg ctcctggagg agatggacac ctatgagtgg gcgctcaaga 2760 gctgggcccc ctgcagcaag gcctgtggag gagggatcca gttcaccaaa tacggctgcc 2820 ggcgcagacg agaccaccac atggtgcagc gacacctgtg tgaccacaag aagaggccca 2880 agcccatccg ccggcgctgc aaccagcacc cgtgctctca gcctgtgtgg gtgacggagg 2940 agtggggtgc ctgcagccgg agctgtggga agctgggggt gcagacacgg gggatacagt 3000 gcctgctgcc cctctccaat ggaacccaca aggtcatgcc ggccaaagcc tgcgccgggg 3060 accggcctga ggcccgacgg ccctgtctcc gagtgccctg cccagcccag tggaggctgg 3120 gagcctggtc ccagtgctct gccacctgtg gagagggcat ccagcagcgg caggtggtgt 3180 gcaggaccaa cgccaacagc ctcgggcatt gcgaggggga taggccagac actgtccagg 3240 tctgcarcct gcccgcctgt ggaggaaatc accagaactc cacggtgagg gccgatgtct 3300 gggaacttgg gacgccagag gggcagtggg tgccacaatc tgraccccta catcccatta 3360 acaagatatc atcaatgtgt gcagcggagc cctgcacggg agacaggtct gtcttctgcc 3420 agatggaagt gctcgatcgc tactgctcca ttcccggcta ccaccggctc tgctgtgtgt 3480 cctgcatcaa gaaggcctcg ggccccaacc ctggcccaga ccctggccca acctcactgc 3540 cccccttctc cactcctgga agccccttac caggacccca ggaccctgca gatgctgcag 3600 agcctcctgg aaagccaacg ggatcagagg accatcagca tggccgagcc acacagctcc 3660 caggagctct ggatacaagc tccccaggga cccagcatcc ctttgcccct gagacaccaa 3720 tccctggagc atcctggagc atctccccta ccacccccgg ggggctgcct tggggctgga 3780 ctcagacacc tacgccagtc cctgaggaca aagggcaacc tggagaagac ctgagacatc 3840 ccggcaccag cctccctgct gacctgcccg ggcggccgcc cgagccctgc catcccactg 3900 gcacgtttac actctgtgta ctgccccgtg actcccagct cagaggacac acatagcagg 3960 gcaggcgcaa gcacagactt cattttaaat cattcgcctt cttctcgttt ggggctgtga 4020 tgctctttac cccacaaagc ggggtgggag gaagacaaag atcagggaaa gccctaatcg 4080 gagatacctc agcaagctgc ccccggcggg actgaccctc tcagggcccc tgttggtctc 4140 ccctgccaag accagggtca actattgctc cctcctcaca gaccctgggc ctgggcaggt 4200 ctgaatcccg gctggtctgt agctrgaagc tgtcagggct gcctgccttc ccggaactgt 4260 gaggacccct gtggagg 4277 24 5724 DNA homo sapiens 24 atgcagtttg tatcctgggc cacactgcta acgctcctgg tgcgggacct ggccgagatg 60 gggagcccag acgccgcggc ggccgtgcgc aaggacaggc tgcacccgag gcaagtgaaa 120 ttattagaga ccctgagcga atacgaaatc gtgtctccca tccgagtgaa cgctctcgga 180 gaaccctttc ccacgaacgt ccacttcaaa agaacgcgac ggagcattaa ctctgccact 240 gacccctggc ctgccttcgc ctcctcctct tcctcctcta cctccwccca ggcgcattac 300 cgcctctctg ccttcggcca gcagtttcta tttaatctca ccgccaatgc cggatttatc 360 gctccactgt tcactgtcac cctcctcggg acgcccgggg tgaatcagac caagttttat 420 tccgaagagg aagcggaact caagcactgt ttctacaaag gctatgtcaa taccaactcc 480 gagcacacgg ccgtcatcag cctctgctca ggaatgctgg gcacattccg gtctcatgat 540 ggggattatt ttattgaacc actacagtct atggatgaac aagaagatga agaggaacaa 600 aacaaacccc acatcattta taggcgcagc gccccccaga gagagccctc aacaggaagg 660 catgcatgtg acacctcaga acacaaaaat aggcacagta aagacaagaa gaaaaccaga 720 gcaagaaaat ggggagaaag gattaacctg gctggtgacg tagcagcatt aaacagcggc 780 ttagcaacag aggcattttc tgcttatggt aataagacgg acaacacaag agaaaagagg 840 acccacagaa ggacaaaacg ttttttatcc tatccacggt ttgtagaagt cttggtggtg 900 gcagacaaca gaatggtttc ataccatgga gaaaaccttc aacactatat tttaacttta 960 atgtcaattg atgggccttc catatctttt aatgctcaga caacattaaa aaacttttgc 1020 cagtggcagc attcgaagaa cagtccaggt ggaatccatc atgatactgc tgttctctta 1080 acaagacagg atatctgcag agctcacgac aaatgtgata ccttaggcct ggctgaactg 1140 ggaaccattt gtgatcccta tagaagctgt tctattagtg aagatagtgg attgagtaca 1200 gcttttacga tcgcccatga gctgggccat gtgtttaaca tgcctcatga tgacaacaac 1260 aaatgtaaag aagaaggagt taagagtccc cagcatgtca tggctccaac actgaacttc 1320 tacaccaacc cctggatgtg gtcaaagtgt agtcgaaaat atatcactga gtttttagac 1380 actggttatg gcgagtgttt gcttaacgaa cctgaatcca gaccctaccc tttgcctgtc 1440 caactgccag gcatccttta caacgtgaat aaacaatgtg aattgatttt tggaccaggt 1500 tctcaggtgt gcccatatat gatgcagtgc agacggctct ggtgcaataa cgtcaatgga 1560 gtacacaaag gctgccggac tcagcacaca ccctgggccg atgggacgga gtgcgagcct 1620 ggaaagcact gcaagtatgg attttgtgtt cccaaagaaa tggatgtccc cgtgacagat 1680 ggatcctggg gaagttggag tccctttgga acctgctcca gaacatgtgg agggggcatc 1740 aaaacagcca ttcgagagtg caacagacca gaaccaaaaa atggtggaaa atactgtgta 1800 ggacgtagaa tgaaatttaa gtcctgcaac acggagccat gtctcaagca gaagcgagac 1860 ttccgagatg aacagtgtgc tcactttgac gggaagcatt ttaacatcaa cggtctgctt 1920 cccaatgtgc gctgggtccc taaatacagt ggaattctga tgaaggaccg gtgcaagttg 1980 ttctgcagag tggcagggaa cacagcctac tatcagcttc gagacagagt gatagatgga 2040 actccttgtg gccaggacac aaatgatatc tgtgtccagg gcctttgccg gcaagctgga 2100 tgcgatcatg ttttaaactc aaaagcccgg agagataaat gtggggtttg tggtggcgat 2160 aattcttcat gcaaaacagt ggcaggaaca tttaatacag tacattatgg ttacaatact 2220 gtggtccgaa ttccagctgg tgctaccaat attgatgtgc ggcagcacag tttctcaggg 2280 gaaacagacg atgacaacta cttagcttta tcaagcagta aaggtgaatt cttgctaaat 2340 ggaaactttg ttgtcacaat ggccaaaagg gaaattcgca ttgggaatgc tgtggtagag 2400 tacagtgggt ccgagactgc cgtagaaaga attaactcaa cagatcgcat tgagcaagaa 2460 cttttgcttc aggttttgtc ggtgggaaag ttgtacaacc ccgatgtacg ctattctttc 2520 aatattccaa ttgaagataa acctcagcag ttttactgga acagtcatgg gccatggcaa 2580 gcatgcagta aaccctgcca aggggaacgg aaacgaaaac ttgtttgcac cagggaatct 2640 gatcagctta ctgtttctga tcaaagatgc gatcggctgc cccagcctgg acacattact 2700 gaaccctgtg gtacagactg tgacctgagg tggcatgttg ccagcaggag tgaatgtagt 2760 gcccagtgtg gcttgggtta ccgcacattg gacatctact gtgccaaata tagcaggctg 2820 gatgggaaga ctgagaaggt tgatgatggt ttttgcagca gccatcccaa accaagcaac 2880 cgtgaaaaat gctcagggga atgtaacacg ggtggctggc gctattctgc ctggactgaa 2940 tgttcaaaaa gctgtgacgg tgggacccag aggagaaggg ctatttgtgt caatacccga 3000 aatgatgtac tggatgacag caaatgcaca catcaagaga aagttaccat tcagaggtgc 3060 agtgagttcc cttgtccaca gtggaaatct ggagactggt cagagtgctt ggtcacctgt 3120 ggaaaagggc ataagcaccg ccaggtctgg tgtcagtttg gtgaagatcg attaaatgat 3180 agaatgtgtg accctgagac caagccaaca tctatgcaga cttgtcagca gccggaatgt 3240 gcatcctggc aggcgggtcc ctggggacag tgcagtgtca cttgtggaca gggataccag 3300 ctaagagcag tgaaatgcat cattgggact tatatgtcag tggtagatga caatgactgt 3360 aatgcagcaa ctagaccaac tgatacccag gactgtgaat taccatcatg tcatcctccc 3420 ccagctgccc cggaaacgag gagaagcaca tacagtgcac caagaaccca gtggcgattt 3480 gggtcttgga ccccatgctc agccacttgt gggaaaggta cccggatgag atacgtcagc 3540 tgccgagatg agaatggctc tgtggctgac gagagtgcct gtgctaccct gcctagacca 3600 gtggcaaagg aagaatgttc tgtgacaccc tgtgggcaat ggaaggcctt ggactggagc 3660 tcttgctctg tgacctgtgg gcaaggtagg gcaacccggc aagtgatgtg tgtcaactac 3720 agtgaccacg tgatygatcg gagtgagtgt gaccaggatt atatcccaga aactgaccag 3780 gactgttcca tgtcaccatg ccctcaaagg accccagaca gtggcttagc tcagcacccc 3840 ttccaaaatg aggactatcg tccccggagc gccagcccca gccgcaccca tgtgctcggt 3900 ggaaaccagt ggagaactgg cccctgggga gcatgttcca gtacctgtgc tggcggatcc 3960 cagcggcgtg ttgttgtatg tcaggatgaa aatggataca ccgcaaacga ctgtgtggag 4020 agaataaaac ctgatgagca aagagcctgt gaatccggcc cttgtcctca gtgggcttat 4080 ggcaactggg gagagtgcac taagctgtgt ggtggaggca taagaacaag actggtggtc 4140 tgtcagcggt ccaacggtga acggtttcca gatttgagct gtgaaattct tgataaacct 4200 cccgatcgtg agcagtgtaa cacacatgct tgtccacacg acgctgcatg gagtactggc 4260 ccttggagct cgtgttctgt ctcttgtggt cgagggcata aacaacgaaa tgtttactgc 4320 atggcaaaag atggaagcca tttagaaagt gattactgta agcacctggc taagccacat 4380 gggcacagaa agtgccgagg aggaagatgc cccaaatgga aagctggcgc ttggagtcag 4440 tgctctgtgt cctgtggccg aggcgtacag cagaggcatg tgggctgtca gatcggaaca 4500 cacaaaatag ccagagagac cgagtgcaac ccatacacca gaccggagtc ggaacgcgac 4560 tgccaaggcc cacggtgtcc cctctacact tggagggcag aggaatggca agaatgcacc 4620 aagacctgcg gcgaaggctc caggtaccgc aaggtggtgt gtgtggatga caacaaaaac 4680 gaggtgcatg gggcacgctg tgacgtgagc aagcggccgg tggaccgtga aagctgtagt 4740 ttgcaaccct gcgagtatgt ctggatcaca ggagaatggt cagagtgctc agtgacctgt 4800 ggaaaaggct acaaacaaag gcttgtctcg tgcagcgaga tttacaccgg gaaggagaat 4860 tatgaataca gctaccaaac caccatcaac tgcccaggca cgcagccccc cagtgttcac 4920 ccctgttacc tgagggactg ccctgtctcg gccacctgga gagttggcaa ctgggggagc 4980 tgctcagtgt cttgtggtgt tggagtgatg cagagatctg tgcaatgttt aaccaatgag 5040 gaccaaccca gccacttatg ccacactgat ctgaagccag aagaacgaaa aacctgccgt 5100 aatgtctata actgtgagtt accccagaat tgcaaggagg taaaaagact taaaggtgcc 5160 agtgaagatg gtgaatattt cctgatgatt agaggaaagc ttctgaagat attctgtgcg 5220 gggatgcact ctgaccaccc caaagagtac gtgacactgg tgcatggaga ctctgagaat 5280 ttctccgagg tttatgggca caggttacac aacccaacag aatgtcccta taacgggagc 5340 cggcgcgatg actgccaatg tcggaaggat tacacggccg ctgggttttc cagttttcag 5400 aaaatcagaa tagacctgac cagcatgcag ataatcacca ctgacttaca gtttgcaagg 5460 acaagcgaag gacatcccgt cccttttgcc acagccgggg attgctacag cgctgccaag 5520 tgcccacagg gtcgttttag catcaacctt tatggaaccg gcttgtcttt aactgaatct 5580 gccagatgga tatcacaagg gaattatgct gtctctgaca tcaagaagtc gccggatggt 5640 acccgagtcg tagggaaatg cggtggttac tgtggaaaat gcactccatc ctctggtact 5700 ggcctggagg tgcgagtttt atag 5724 25 1907 PRT homo sapiens 25 Met Gln Phe Val Ser Trp Ala Thr Leu Leu Thr Leu Leu Val Arg Asp 1 5 10 15 Leu Ala Glu Met Gly Ser Pro Asp Ala Ala Ala Ala Val Arg Lys Asp 20 25 30 Arg Leu His Pro Arg Gln Val Lys Leu Leu Glu Thr Leu Ser Glu Tyr 35 40 45 Glu Ile Val Ser Pro Ile Arg Val Asn Ala Leu Gly Glu Pro Phe Pro 50 55 60 Thr Asn Val His Phe Lys Arg Thr Arg Arg Ser Ile Asn Ser Ala Thr 65 70 75 80 Asp Pro Trp Pro Ala Phe Ala Ser Ser Ser Ser Ser Ser Thr Ser Ser 85 90 95 Gln Ala His Tyr Arg Leu Ser Ala Phe Gly Gln Gln Phe Leu Phe Asn 100 105 110 Leu Thr Ala Asn Ala Gly Phe Ile Ala Pro Leu Phe Thr Val Thr Leu 115 120 125 Leu Gly Thr Pro Gly Val Asn Gln Thr Lys Phe Tyr Ser Glu Glu Glu 130 135 140 Ala Glu Leu Lys His Cys Phe Tyr Lys Gly Tyr Val Asn Thr Asn Ser 145 150 155 160 Glu His Thr Ala Val Ile Ser Leu Cys Ser Gly Met Leu Gly Thr Phe 165 170 175 Arg Ser His Asp Gly Asp Tyr Phe Ile Glu Pro Leu Gln Ser Met Asp 180 185 190 Glu Gln Glu Asp Glu Glu Glu Gln Asn Lys Pro His Ile Ile Tyr Arg 195 200 205 Arg Ser Ala Pro Gln Arg Glu Pro Ser Thr Gly Arg His Ala Cys Asp 210 215 220 Thr Ser Glu His Lys Asn Arg His Ser Lys Asp Lys Lys Lys Thr Arg 225 230 235 240 Ala Arg Lys Trp Gly Glu Arg Ile Asn Leu Ala Gly Asp Val Ala Ala 245 250 255 Leu Asn Ser Gly Leu Ala Thr Glu Ala Phe Ser Ala Tyr Gly Asn Lys 260 265 270 Thr Asp Asn Thr Arg Glu Lys Arg Thr His Arg Arg Thr Lys Arg Phe 275 280 285 Leu Ser Tyr Pro Arg Phe Val Glu Val Leu Val Val Ala Asp Asn Arg 290 295 300 Met Val Ser Tyr His Gly Glu Asn Leu Gln His Tyr Ile Leu Thr Leu 305 310 315 320 Met Ser Ile Asp Gly Pro Ser Ile Ser Phe Asn Ala Gln Thr Thr Leu 325 330 335 Lys Asn Phe Cys Gln Trp Gln His Ser Lys Asn Ser Pro Gly Gly Ile 340 345 350 His His Asp Thr Ala Val Leu Leu Thr Arg Gln Asp Ile Cys Arg Ala 355 360 365 His Asp Lys Cys Asp Thr Leu Gly Leu Ala Glu Leu Gly Thr Ile Cys 370 375 380 Asp Pro Tyr Arg Ser Cys Ser Ile Ser Glu Asp Ser Gly Leu Ser Thr 385 390 395 400 Ala Phe Thr Ile Ala His Glu Leu Gly His Val Phe Asn Met Pro His 405 410 415 Asp Asp Asn Asn Lys Cys Lys Glu Glu Gly Val Lys Ser Pro Gln His 420 425 430 Val Met Ala Pro Thr Leu Asn Phe Tyr Thr Asn Pro Trp Met Trp Ser 435 440 445 Lys Cys Ser Arg Lys Tyr Ile Thr Glu Phe Leu Asp Thr Gly Tyr Gly 450 455 460 Glu Cys Leu Leu Asn Glu Pro Glu Ser Arg Pro Tyr Pro Leu Pro Val 465 470 475 480 Gln Leu Pro Gly Ile Leu Tyr Asn Val Asn Lys Gln Cys Glu Leu Ile 485 490 495 Phe Gly Pro Gly Ser Gln Val Cys Pro Tyr Met Met Gln Cys Arg Arg 500 505 510 Leu Trp Cys Asn Asn Val Asn Gly Val His Lys Gly Cys Arg Thr Gln 515 520 525 His Thr Pro Trp Ala Asp Gly Thr Glu Cys Glu Pro Gly Lys His Cys 530 535 540 Lys Tyr Gly Phe Cys Val Pro Lys Glu Met Asp Val Pro Val Thr Asp 545 550 555 560 Gly Ser Trp Gly Ser Trp Ser Pro Phe Gly Thr Cys Ser Arg Thr Cys 565 570 575 Gly Gly Gly Ile Lys Thr Ala Ile Arg Glu Cys Asn Arg Pro Glu Pro 580 585 590 Lys Asn Gly Gly Lys Tyr Cys Val Gly Arg Arg Met Lys Phe Lys Ser 595 600 605 Cys Asn Thr Glu Pro Cys Leu Lys Gln Lys Arg Asp Phe Arg Asp Glu 610 615 620 Gln Cys Ala His Phe Asp Gly Lys His Phe Asn Ile Asn Gly Leu Leu 625 630 635 640 Pro Asn Val Arg Trp Val Pro Lys Tyr Ser Gly Ile Leu Met Lys Asp 645 650 655 Arg Cys Lys Leu Phe Cys Arg Val Ala Gly Asn Thr Ala Tyr Tyr Gln 660 665 670 Leu Arg Asp Arg Val Ile Asp Gly Thr Pro Cys Gly Gln Asp Thr Asn 675 680 685 Asp Ile Cys Val Gln Gly Leu Cys Arg Gln Ala Gly Cys Asp His Val 690 695 700 Leu Asn Ser Lys Ala Arg Arg Asp Lys Cys Gly Val Cys Gly Gly Asp 705 710 715 720 Asn Ser Ser Cys Lys Thr Val Ala Gly Thr Phe Asn Thr Val His Tyr 725 730 735 Gly Tyr Asn Thr Val Val Arg Ile Pro Ala Gly Ala Thr Asn Ile Asp 740 745 750 Val Arg Gln His Ser Phe Ser Gly Glu Thr Asp Asp Asp Asn Tyr Leu 755 760 765 Ala Leu Ser Ser Ser Lys Gly Glu Phe Leu Leu Asn Gly Asn Phe Val 770 775 780 Val Thr Met Ala Lys Arg Glu Ile Arg Ile Gly Asn Ala Val Val Glu 785 790 795 800 Tyr Ser Gly Ser Glu Thr Ala Val Glu Arg Ile Asn Ser Thr Asp Arg 805 810 815 Ile Glu Gln Glu Leu Leu Leu Gln Val Leu Ser Val Gly Lys Leu Tyr 820 825 830 Asn Pro Asp Val Arg Tyr Ser Phe Asn Ile Pro Ile Glu Asp Lys Pro 835 840 845 Gln Gln Phe Tyr Trp Asn Ser His Gly Pro Trp Gln Ala Cys Ser Lys 850 855 860 Pro Cys Gln Gly Glu Arg Lys Arg Lys Leu Val Cys Thr Arg Glu Ser 865 870 875 880 Asp Gln Leu Thr Val Ser Asp Gln Arg Cys Asp Arg Leu Pro Gln Pro 885 890 895 Gly His Ile Thr Glu Pro Cys Gly Thr Asp Cys Asp Leu Arg Trp His 900 905 910 Val Ala Ser Arg Ser Glu Cys Ser Ala Gln Cys Gly Leu Gly Tyr Arg 915 920 925 Thr Leu Asp Ile Tyr Cys Ala Lys Tyr Ser Arg Leu Asp Gly Lys Thr 930 935 940 Glu Lys Val Asp Asp Gly Phe Cys Ser Ser His Pro Lys Pro Ser Asn 945 950 955 960 Arg Glu Lys Cys Ser Gly Glu Cys Asn Thr Gly Gly Trp Arg Tyr Ser 965 970 975 Ala Trp Thr Glu Cys Ser Lys Ser Cys Asp Gly Gly Thr Gln Arg Arg 980 985 990 Arg Ala Ile Cys Val Asn Thr Arg Asn Asp Val Leu Asp Asp Ser Lys 995 1000 1005 Cys Thr His Gln Glu Lys Val Thr Ile Gln Arg Cys Ser Glu Phe Pro 1010 1015 1020 Cys Pro Gln Trp Lys Ser Gly Asp Trp Ser Glu Cys Leu Val Thr Cys 1025 1030 1035 1040 Gly Lys Gly His Lys His Arg Gln Val Trp Cys Gln Phe Gly Glu Asp 1045 1050 1055 Arg Leu Asn Asp Arg Met Cys Asp Pro Glu Thr Lys Pro Thr Ser Met 1060 1065 1070 Gln Thr Cys Gln Gln Pro Glu Cys Ala Ser Trp Gln Ala Gly Pro Trp 1075 1080 1085 Gly Gln Cys Ser Val Thr Cys Gly Gln Gly Tyr Gln Leu Arg Ala Val 1090 1095 1100 Lys Cys Ile Ile Gly Thr Tyr Met Ser Val Val Asp Asp Asn Asp Cys 1105 1110 1115 1120 Asn Ala Ala Thr Arg Pro Thr Asp Thr Gln Asp Cys Glu Leu Pro Ser 1125 1130 1135 Cys His Pro Pro Pro Ala Ala Pro Glu Thr Arg Arg Ser Thr Tyr Ser 1140 1145 1150 Ala Pro Arg Thr Gln Trp Arg Phe Gly Ser Trp Thr Pro Cys Ser Ala 1155 1160 1165 Thr Cys Gly Lys Gly Thr Arg Met Arg Tyr Val Ser Cys Arg Asp Glu 1170 1175 1180 Asn Gly Ser Val Ala Asp Glu Ser Ala Cys Ala Thr Leu Pro Arg Pro 1185 1190 1195 1200 Val Ala Lys Glu Glu Cys Ser Val Thr Pro Cys Gly Gln Trp Lys Ala 1205 1210 1215 Leu Asp Trp Ser Ser Cys Ser Val Thr Cys Gly Gln Gly Arg Ala Thr 1220 1225 1230 Arg Gln Val Met Cys Val Asn Tyr Ser Asp His Val Ile Asp Arg Ser 1235 1240 1245 Glu Cys Asp Gln Asp Tyr Ile Pro Glu Thr Asp Gln Asp Cys Ser Met 1250 1255 1260 Ser Pro Cys Pro Gln Arg Thr Pro Asp Ser Gly Leu Ala Gln His Pro 1265 1270 1275 1280 Phe Gln Asn Glu Asp Tyr Arg Pro Arg Ser Ala Ser Pro Ser Arg Thr 1285 1290 1295 His Val Leu Gly Gly Asn Gln Trp Arg Thr Gly Pro Trp Gly Ala Cys 1300 1305 1310 Ser Ser Thr Cys Ala Gly Gly Ser Gln Arg Arg Val Val Val Cys Gln 1315 1320 1325 Asp Glu Asn Gly Tyr Thr Ala Asn Asp Cys Val Glu Arg Ile Lys Pro 1330 1335 1340 Asp Glu Gln Arg Ala Cys Glu Ser Gly Pro Cys Pro Gln Trp Ala Tyr 1345 1350 1355 1360 Gly Asn Trp Gly Glu Cys Thr Lys Leu Cys Gly Gly Gly Ile Arg Thr 1365 1370 1375 Arg Leu Val Val Cys Gln Arg Ser Asn Gly Glu Arg Phe Pro Asp Leu 1380 1385 1390 Ser Cys Glu Ile Leu Asp Lys Pro Pro Asp Arg Glu Gln Cys Asn Thr 1395 1400 1405 His Ala Cys Pro His Asp Ala Ala Trp Ser Thr Gly Pro Trp Ser Ser 1410 1415 1420 Cys Ser Val Ser Cys Gly Arg Gly His Lys Gln Arg Asn Val Tyr Cys 1425 1430 1435 1440 Met Ala Lys Asp Gly Ser His Leu Glu Ser Asp Tyr Cys Lys His Leu 1445 1450 1455 Ala Lys Pro His Gly His Arg Lys Cys Arg Gly Gly Arg Cys Pro Lys 1460 1465 1470 Trp Lys Ala Gly Ala Trp Ser Gln Cys Ser Val Ser Cys Gly Arg Gly 1475 1480 1485 Val Gln Gln Arg His Val Gly Cys Gln Ile Gly Thr His Lys Ile Ala 1490 1495 1500 Arg Glu Thr Glu Cys Asn Pro Tyr Thr Arg Pro Glu Ser Glu Arg Asp 1505 1510 1515 1520 Cys Gln Gly Pro Arg Cys Pro Leu Tyr Thr Trp Arg Ala Glu Glu Trp 1525 1530 1535 Gln Glu Cys Thr Lys Thr Cys Gly Glu Gly Ser Arg Tyr Arg Lys Val 1540 1545 1550 Val Cys Val Asp Asp Asn Lys Asn Glu Val His Gly Ala Arg Cys Asp 1555 1560 1565 Val Ser Lys Arg Pro Val Asp Arg Glu Ser Cys Ser Leu Gln Pro Cys 1570 1575 1580 Glu Tyr Val Trp Ile Thr Gly Glu Trp Ser Glu Cys Ser Val Thr Cys 1585 1590 1595 1600 Gly Lys Gly Tyr Lys Gln Arg Leu Val Ser Cys Ser Glu Ile Tyr Thr 1605 1610 1615 Gly Lys Glu Asn Tyr Glu Tyr Ser Tyr Gln Thr Thr Ile Asn Cys Pro 1620 1625 1630 Gly Thr Gln Pro Pro Ser Val His Pro Cys Tyr Leu Arg Asp Cys Pro 1635 1640 1645 Val Ser Ala Thr Trp Arg Val Gly Asn Trp Gly Ser Cys Ser Val Ser 1650 1655 1660 Cys Gly Val Gly Val Met Gln Arg Ser Val Gln Cys Leu Thr Asn Glu 1665 1670 1675 1680 Asp Gln Pro Ser His Leu Cys His Thr Asp Leu Lys Pro Glu Glu Arg 1685 1690 1695 Lys Thr Cys Arg Asn Val Tyr Asn Cys Glu Leu Pro Gln Asn Cys Lys 1700 1705 1710 Glu Val Lys Arg Leu Lys Gly Ala Ser Glu Asp Gly Glu Tyr Phe Leu 1715 1720 1725 Met Ile Arg Gly Lys Leu Leu Lys Ile Phe Cys Ala Gly Met His Ser 1730 1735 1740 Asp His Pro Lys Glu Tyr Val Thr Leu Val His Gly Asp Ser Glu Asn 1745 1750 1755 1760 Phe Ser Glu Val Tyr Gly His Arg Leu His Asn Pro Thr Glu Cys Pro 1765 1770 1775 Tyr Asn Gly Ser Arg Arg Asp Asp Cys Gln Cys Arg Lys Asp Tyr Thr 1780 1785 1790 Ala Ala Gly Phe Ser Ser Phe Gln Lys Ile Arg Ile Asp Leu Thr Ser 1795 1800 1805 Met Gln Ile Ile Thr Thr Asp Leu Gln Phe Ala Arg Thr Ser Glu Gly 1810 1815 1820 His Pro Val Pro Phe Ala Thr Ala Gly Asp Cys Tyr Ser Ala Ala Lys 1825 1830 1835 1840 Cys Pro Gln Gly Arg Phe Ser Ile Asn Leu Tyr Gly Thr Gly Leu Ser 1845 1850 1855 Leu Thr Glu Ser Ala Arg Trp Ile Ser Gln Gly Asn Tyr Ala Val Ser 1860 1865 1870 Asp Ile Lys Lys Ser Pro Asp Gly Thr Arg Val Val Gly Lys Cys Gly 1875 1880 1885 Gly Tyr Cys Gly Lys Cys Thr Pro Ser Ser Gly Thr Gly Leu Glu Val 1890 1895 1900 Arg Val Leu 1905 26 6060 DNA homo sapiens 26 ccggcgcgcc tcggagcgca agttcctcgc cttctcctgc ccgctcgctg ggcattatgc 60 ggccaagcag ccgagcccca gtcctcctcc tcctcctgct cctccggctc ctcctgcggg 120 cccgagcggc tcagctctcg gcaggcggcg gcgttgttca gccgagcgca gacgggaccc 180 tcgcagcgag acctcaagcg actcctaaag tcaaaagttg gcggcgggcg ccgggctccg 240 cgcgctctcc acggccgctg cctcgcgtcg ccgccgcagc caaggagggc aggagggagg 300 ggggtggggg cagcggaggg aggggtggga agcaccatgc agtttgtatc ctgggccaca 360 ctgctaacgc tcctggtgcg ggacctggcc gagatgggga gcccagacgc cgcggcggcc 420 gtgcgcaagg acaggctgca cccgaggcaa gtgaaattat tagagaccct gagcgaatac 480 gaaatcgtgt ctcccatccg agtgaacgct ctcggagaac cctttcccac gaacgtccac 540 ttcaaaagaa cgcgacggag cattaactct gccactgacc cctggcctgc cttcgcctcc 600 tcctcttcct cctctacctc cwcccaggcg cattaccgcc tctctgcctt cggccagcag 660 tttctattta atctcaccgc caatgccgga tttatcgctc cactgttcac tgtcaccctc 720 ctcgggacgc ccggggtgaa tcagaccaag ttttattccg aagaggaagc ggaactcaag 780 cactgtttct acaaaggcta tgtcaatacc aactccgagc acacggccgt catcagcctc 840 tgctcaggaa tgctgggcac attccggtct catgatgggg attattttat tgaaccacta 900 cagtctatgg atgaacaaga agatgaagag gaacaaaaca aaccccacat catttatagg 960 cgcagcgccc cccagagaga gccctcaaca ggaaggcatg catgtgacac ctcagaacac 1020 aaaaataggc acagtaaaga caagaagaaa accagagcaa gaaaatgggg agaaaggatt 1080 aacctggctg gtgacgtagc agcattaaac agcggcttag caacagaggc attttctgct 1140 tatggtaata agacggacaa cacaagagaa aagaggaccc acagaaggac aaaacgtttt 1200 ttatcctatc cacggtttgt agaagtcttg gtggtggcag acaacagaat ggtttcatac 1260 catggagaaa accttcaaca ctatatttta actttaatgt caattgatgg gccttccata 1320 tcttttaatg ctcagacaac attaaaaaac ttttgccagt ggcagcattc gaagaacagt 1380 ccaggtggaa tccatcatga tactgctgtt ctcttaacaa gacaggatat ctgcagagct 1440 cacgacaaat gtgatacctt aggcctggct gaactgggaa ccatttgtga tccctataga 1500 agctgttcta ttagtgaaga tagtggattg agtacagctt ttacgatcgc ccatgagctg 1560 ggccatgtgt ttaacatgcc tcatgatgac aacaacaaat gtaaagaaga aggagttaag 1620 agtccccagc atgtcatggc tccaacactg aacttctaca ccaacccctg gatgtggtca 1680 aagtgtagtc gaaaatatat cactgagttt ttagacactg gttatggcga gtgtttgctt 1740 aacgaacctg aatccagacc ctaccctttg cctgtccaac tgccaggcat cctttacaac 1800 gtgaataaac aatgtgaatt gatttttgga ccaggttctc aggtgtgccc atatatgatg 1860 cagtgcagac ggctctggtg caataacgtc aatggagtac acaaaggctg ccggactcag 1920 cacacaccct gggccgatgg gacggagtgc gagcctggaa agcactgcaa gtatggattt 1980 tgtgttccca aagaaatgga tgtccccgtg acagatggat cctggggaag ttggagtccc 2040 tttggaacct gctccagaac atgtggaggg ggcatcaaaa cagccattcg agagtgcaac 2100 agaccagaac caaaaaatgg tggaaaatac tgtgtaggac gtagaatgaa atttaagtcc 2160 tgcaacacgg agccatgtct caagcagaag cgagacttcc gagatgaaca gtgtgctcac 2220 tttgacggga agcattttaa catcaacggt ctgcttccca atgtgcgctg ggtccctaaa 2280 tacagtggaa ttctgatgaa ggaccggtgc aagttgttct gcagagtggc agggaacaca 2340 gcctactatc agcttcgaga cagagtgata gatggaactc cttgtggcca ggacacaaat 2400 gatatctgtg tccagggcct ttgccggcaa gctggatgcg atcatgtttt aaactcaaaa 2460 gcccggagag ataaatgtgg ggtttgtggt ggcgataatt cttcatgcaa aacagtggca 2520 ggaacattta atacagtaca ttatggttac aatactgtgg tccgaattcc agctggtgct 2580 accaatattg atgtgcggca gcacagtttc tcaggggaaa cagacgatga caactactta 2640 gctttatcaa gcagtaaagg tgaattcttg ctaaatggaa actttgttgt cacaatggcc 2700 aaaagggaaa ttcgcattgg gaatgctgtg gtagagtaca gtgggtccga gactgccgta 2760 gaaagaatta actcaacaga tcgcattgag caagaacttt tgcttcaggt tttgtcggtg 2820 ggaaagttgt acaaccccga tgtacgctat tctttcaata ttccaattga agataaacct 2880 cagcagtttt actggaacag tcatgggcca tggcaagcat gcagtaaacc ctgccaaggg 2940 gaacggaaac gaaaacttgt ttgcaccagg gaatctgatc agcttactgt ttctgatcaa 3000 agatgcgatc ggctgcccca gcctggacac attactgaac cctgtggtac agactgtgac 3060 ctgaggtggc atgttgccag caggagtgaa tgtagtgccc agtgtggctt gggttaccgc 3120 acattggaca tctactgtgc caaatatagc aggctggatg ggaagactga gaaggttgat 3180 gatggttttt gcagcagcca tcccaaacca agcaaccgtg aaaaatgctc aggggaatgt 3240 aacacgggtg gctggcgcta ttctgcctgg actgaatgtt caaaaagctg tgacggtggg 3300 acccagagga gaagggctat ttgtgtcaat acccgaaatg atgtactgga tgacagcaaa 3360 tgcacacatc aagagaaagt taccattcag aggtgcagtg agttcccttg tccacagtgg 3420 aaatctggag actggtcaga gtgcttggtc acctgtggaa aagggcataa gcaccgccag 3480 gtctggtgtc agtttggtga agatcgatta aatgatagaa tgtgtgaccc tgagaccaag 3540 ccaacatcta tgcagacttg tcagcagccg gaatgtgcat cctggcaggc gggtccctgg 3600 ggacagtgca gtgtcacttg tggacaggga taccagctaa gagcagtgaa atgcatcatt 3660 gggacttata tgtcagtggt agatgacaat gactgtaatg cagcaactag accaactgat 3720 acccaggact gtgaattacc atcatgtcat cctcccccag ctgccccgga aacgaggaga 3780 agcacataca gtgcaccaag aacccagtgg cgatttgggt cttggacccc atgctcagcc 3840 acttgtggga aaggtacccg gatgagatac gtcagctgcc gagatgagaa tggctctgtg 3900 gctgacgaga gtgcctgtgc taccctgcct agaccagtgg caaaggaaga atgttctgtg 3960 acaccctgtg ggcaatggaa ggccttggac tggagctctt gctctgtgac ctgtgggcaa 4020 ggtagggcaa cccggcaagt gatgtgtgtc aactacagtg accacgtgat ygatcggagt 4080 gagtgtgacc aggattatat cccagaaact gaccaggact gttccatgtc accatgccct 4140 caaaggaccc cagacagtgg cttagctcag caccccttcc aaaatgagga ctatcgtccc 4200 cggagcgcca gccccagccg cacccatgtg ctcggtggaa accagtggag aactggcccc 4260 tggggagcat gttccagtac ctgtgctggc ggatcccagc ggcgtgttgt tgtatgtcag 4320 gatgaaaatg gatacaccgc aaacgactgt gtggagagaa taaaacctga tgagcaaaga 4380 gcctgtgaat ccggcccttg tcctcagtgg gcttatggca actggggaga gtgcactaag 4440 ctgtgtggtg gaggcataag aacaagactg gtggtctgtc agcggtccaa cggtgaacgg 4500 tttccagatt tgagctgtga aattcttgat aaacctcccg atcgtgagca gtgtaacaca 4560 catgcttgtc cacacgacgc tgcatggagt actggccctt ggagctcgtg ttctgtctct 4620 tgtggtcgag ggcataaaca acgaaatgtt tactgcatgg caaaagatgg aagccattta 4680 gaaagtgatt actgtaagca cctggctaag ccacatgggc acagaaagtg ccgaggagga 4740 agatgcccca aatggaaagc tggcgcttgg agtcagtgct ctgtgtcctg tggccgaggc 4800 gtacagcaga ggcatgtggg ctgtcagatc ggaacacaca aaatagccag agagaccgag 4860 tgcaacccat acaccagacc ggagtcggaa cgcgactgcc aaggcccacg gtgtcccctc 4920 tacacttgga gggcagagga atggcaagaa tgcaccaaga cctgcggcga aggctccagg 4980 taccgcaagg tggtgtgtgt ggatgacaac aaaaacgagg tgcatggggc acgctgtgac 5040 gtgagcaagc ggccggtgga ccgtgaaagc tgtagtttgc aaccctgcga gtatgtctgg 5100 atcacaggag aatggtcaga gtgctcagtg acctgtggaa aaggctacaa acaaaggctt 5160 gtctcgtgca gcgagattta caccgggaag gagaattatg aatacagcta ccaaaccacc 5220 atcaactgcc caggcacgca gccccccagt gttcacccct gttacctgag ggactgccct 5280 gtctcggcca cctggagagt tggcaactgg gggagctgct cagtgtcttg tggtgttgga 5340 gtgatgcaga gatctgtgca atgtttaacc aatgaggacc aacccagcca cttatgccac 5400 actgatctga agccagaaga acgaaaaacc tgccgtaatg tctataactg tgagttaccc 5460 cagaattgca aggaggtaaa aagacttaaa ggtgccagtg aagatggtga atatttcctg 5520 atgattagag gaaagcttct gaagatattc tgtgcgggga tgcactctga ccaccccaaa 5580 gagtacgtga cactggtgca tggagactct gagaatttct ccgaggttta tgggcacagg 5640 ttacacaacc caacagaatg tccctataac gggagccggc gcgatgactg ccaatgtcgg 5700 aaggattaca cggccgctgg gttttccagt tttcagaaaa tcagaataga cctgaccagc 5760 atgcagataa tcaccactga cttacagttt gcaaggacaa gcgaaggaca tcccgtccct 5820 tttgccacag ccggggattg ctacagcgct gccaagtgcc cacagggtcg ttttagcatc 5880 aacctttatg gaaccggctt gtctttaact gaatctgcca gatggatatc acaagggaat 5940 tatgctgtct ctgacatcaa gaagtcgccg gatggtaccc gagtcgtagg gaaatgcggt 6000 ggttactgtg gaaaatgcac tccatcctct ggtactggcc tggaggtgcg agttttatag 6060 

What is claimed is:
 1. An isolated nucleic acid molecule comprising at a nucleotide sequence encoding an amino acid sequence drawn from the group consisting of SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and
 25. 2. An isolated nucleic acid molecule comprising a nucleotide sequence that: (a) encodes the amino acid sequence shown in SEQ ID NO: 20; and (b) hybridizes under stringent conditions to the nucleotide sequence of SEQ ID NO: 19 or the complement thereof.
 3. An isolated nucleic acid molecule according to claim 2 wherein said nucleotide sequence is present in cDNA.
 4. An isolated nucleic acid molecule encoding the amino acid sequence presented in SEQ ID NO:20.
 5. An isolated nucleic acid molecule encoding the amino acid sequence presented in SEQ ID NO:22.
 6. An isolated nucleic acid molecule encoding the amino acid sequence presented in SEQ ID NO:25. 